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Play Episode Listen Later Jun 27, 2024 34:54

Dr. Neeraj Agarwal and Dr. Rana McKay discuss promising studies in GU cancers featured at the 2024 ASCO Annual Meeting that highlighted improved outcomes in urothelial carcinoma, improved survival in renal cell carcinoma, and the role of ctDNA as a potential biomarker for predicting outcomes. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I am delighted to welcome Dr. Rana McKay, a GU medical oncologist and associate professor at the University of California San Diego. Today, we'll be discussing some key GU abstracts featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Rana, we're thrilled to have you on the podcast today to share your insights on key advances in GU oncology from ASCO24. Dr. Rana McKay: Thank you so much, Neeraj; it's a pleasure to be here. Dr. Neeraj Agarwal: So, Rana, let's start with some bladder cancer abstracts. Could you tell us about Abstract 4503, titled “Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer”? Dr. Rana McKay: Of course, I would be delighted to. First, I would like to remind our listeners that enfortumab vedotin (EV) was approved as a monotherapy for the treatment of locally advanced or metastatic urothelial cancer based on the results of EV-201 and EV-301 trials. In these pivotal studies, EV was initiated at a dose of 1.25 mg/kg, and dose modifications, such as reductions and interruptions, were used to manage adverse events. In the abstract presented at ASCO 2024, Dr. Daniel Petrylak and colleagues conducted a post-hoc exploratory analysis to evaluate the association between EV plasma exposure and outcomes. They used multiple pharmacokinetic samples collected during the first two cycles and pre-dose samples from 3 EV monotherapy studies, namely EV-101, EV-201, and EV-301, that were conducted in patients with previously treated locally advanced or metastatic urothelial carcinoma. Dose reductions to 1 mg/kg were required in 42.1% and 35.1% of patients in the EV-201 and EV-301 trials, respectively, and reductions to 0.75 mg/kg were required in 13.6% and 11.1% in the EV-201 and EV-301 trials, respectively. Higher EV exposure during the first two cycles was associated with a higher objective response rate. The ORR was 21.4% for the dose of 0.75 mg/kg, while it was 18.5% for the dose of 1.0 mg/kg. Interestingly, increasing the dosage to 1.25 mg/kg improved the ORR, which ranged from 40 to 51.1% across various studies. In the EV-301 trial, when comparing the efficacy of EV to chemotherapy, EV improved PFS and OS across all dose quartiles, and there was no evidence that recommended dose modifications impacted long-term efficacy outcomes. Dr. Neeraj Agarwal: Thank you, Rana, for this great summary. I would like to add that the meticulously conducted pharmacokinetic studies demonstrated that serum levels of EV correlated with responses. Importantly, patients who had to decrease the dose did not experience compromised outcomes as EV improved PFS and OS outcomes vs chemotherapy in across all exposure quartiles in the EV-301 trial where EV was compared with chemotherapy. These findings highlight the need to start at the recommended dose of 1.25 mg/kg and reduce it, if necessary, however, clinicians should not start at a lower dose. Dr. Rana McKay: I totally agree with you, Neeraj. Now, moving on to a different setting in bladder cancer, what can you tell us about LBA4517, titled “Perioperative sacituzumab govitecan alone or in combination with pembrolizumab for patients with muscle-invasive urothelial bladder cancer: SURE-01/02 interim results”? Dr. Neeraj Agarwal: Of course! So, SURE was a multicohort, open-label, phase 2 study in patients with muscle-invasive bladder cancer assessing sacituzumab govitecan as a neoadjuvant therapy either alone in SURE-01 or as a combination with pembrolizumab followed by adjuvant pembro in SURE-02 in a flexible design allowing a bladder-sparing approach. In the abstract presented at ASCO 2024, Dr. Antonio Cigliola and colleagues report interim results of the SURE-01 study. Patients with cT2-4N0M0 urothelial carcinoma who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy were planned to receive 4 cycles of neoadjuvant sacituzumab govitecan at a dose of 10 mg/kg followed by radical cystectomy. An extensive assessment was performed at baseline and after the 4 cycles for response assessment. Patients with clinical complete response defined with negative MRI, cystoscopy and ctDNA assays refusing radical cystectomy were offered redo transurethral resection of the bladder tumor or repeat TURBT followed by observation in the absence of viable high-grade tumor in the bladder. The primary endpoint was pathological complete response rate, while secondary endpoints included pathological downstaging rate and safety. After the first 8 patients were enrolled, the protocol was amended due to the occurrence of grade 3 and 4 neutropenia and diarrhea in 75% and 50% of patients, respectively, and 2 deaths – one of which was deemed to be treatment-related due to sepsis. Key protocol changes included the reduction of the dose of sacituzumab govitecan to 7.5 mg/kg, the introduction of G-CSF as primary prophylaxis, and the exclusion of patients at high risk of febrile neutropenia per ASCO guidelines. Among 21 patients who received at least one cycle of sacituzumab govitecan and included in the intention-to-treat population, 47.6% had a complete pathological response, and 52.4% had pathological downstaging. 11 patients underwent radical cystectomy, while 7 received repeat-TURBT due to complete clinical response or patient preference. Regarding the safety profile, grade 3 or more adverse events occurred in 42.5% of patients. Treatment-related adverse events leading to dose interruptions or discontinuations were more common before the protocol amendment. It is noteworthy that 3 patients died after treatment discontinuation, with one deemed treatment-related, as previously mentioned. Dr. Rana McKay: Thank you, Neeraj, for a great summary. The pathological complete responses observed show promising activity for sacituzumab govitecan as a neo-adjuvant therapy and a window for bladder-sparing approaches, which is definitely exciting news for our patients! However, although the 3 deaths encountered in a neo-adjuvant setting could be concerning, the improvement of the safety profile after protocol amendments is reassuring and supports the continuation of the study. Dr. Neeraj Agarwal: Before wrapping up the bladder cancer section, would you like to share your insights with our listeners on Abstract 4518, titled “Quantitative circulating tumor DNA (ctDNA) assessment in patients with advanced urothelial carcinoma treated with pembrolizumab or platinum-based chemotherapy from the phase 3 KEYNOTE-361 trial”? Dr. Rana McKay: Sure. So, the KEYNOTE-361 trial was a randomized phase 3 study with 3 arms that included pembrolizumab plus chemotherapy, pembrolizumab monotherapy, or chemotherapy alone in patients with previously untreated advanced urothelial carcinoma. The results showed that neither the combination of pembrolizumab plus chemotherapy nor pembrolizumab monotherapy improved survival outcomes compared to the chemotherapy arm. So, in this exploratory analysis presented at ASCO24, Dr. Tom Powles and colleagues sought to assess the role of ctDNA as a potential biomarker between the pembrolizumab monotherapy arm and the chemotherapy arm. Tumor tissue mutations were evaluated using whole exome sequencing, and plasma ctDNA was assessed with the Guardant 360 assay. Changes in ctDNA from pre-treatment cycle 1 to on-treatment cycle 2, so 3 weeks post-baseline assessment, were quantified by the maximum variant allele frequency of tumor tissue-specific mutations. Results showed that lower baseline ctDNA levels were associated with improved clinical outcomes of response in the pembrolizumab arm but not in the chemotherapy arm. This improvement in the pembrolizumab arm was also robust to adjustment for tumor mutational burden and PD-L1. Additionally, chemotherapy led to a ctDNA clearance rate of 41% compared to 11% in the pembrolizumab arm. Patients who had a large ctDNA reduction with pembrolizumab had significantly improved outcomes compared to those achieving a large reduction with chemotherapy with a hazard ratio of 0.25. However, this did not replicate in patients who did not achieve a large reduction, as these patients had similar outcomes across both arms. Let's switch gears to kidney cancer and start with Abstract 4508, reporting the final OS analysis from the JAVELIN Renal-101 trial. Neeraj, what would you like to tell us about this abstract? Dr. Neeraj Agarwal: Well, as a quick reminder, the JAVELIN Renal-101 was a randomized phase 3 trial where patients with previously untreated advanced or metastatic clear cell renal cell carcinoma were randomized to receive either the combination of avelumab plus axitinib or sunitinib. In previous analyses, the combination of avelumab and axitinib significantly improved PFS compared to sunitinib and was subsequently approved by the FDA for the first-line treatment of patients with advanced RCC in 2019. This superiority in PFS was maintained across the different analyses; however, OS data remained immature. In the abstract presented at ASCO24 by Dr. Robert Motzer from Memorial Sloan Kettering Cancer Center and colleagues, the authors reported OS results at a median follow-up of around 73 months and a minimum of 68 months for all patients, which is the longest follow-up for any ICI-TKI combination in RCC. The final analysis in the overall population favored the combination of avelumab plus axitinib with a median OS of 44.8 months compared to 38.9 months with sunitinib, however, this did not reach statistical significance with a hazard ratio of 0.88. The PFS results and safety profile were consistent with previous analyses. Dr. Rana McKay: Thank you, Neeraj, for such a nice overview of this abstract. These new data could make this regimen less optimal than other ICI-TKI combinations in the first-line mRCC setting. Dr. Neeraj Agarwal: I concur, Rana. Moving on to perhaps one of the most exciting GU abstracts featured, Abstract 4506, titled “Circulating kidney injury molecule-1 biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection.” Rana, what are your thoughts on this abstract? Dr. Rana McKay: Well, first, I would like to take a step back and remind our audience that in the IMmotion010 trial, patients with resected intermediate to high-risk RCC with clear cell and/or sarcomatoid component were randomized in a 1:1 ratio to receive either atezolizumab or placebo. Investigator-assessed disease-free survival, which was the primary endpoint, favored the atezolizumab arm but did not reach statistical significance. In the abstract featured at ASCO24, Dr. Laurence Albiges and colleagues build on data previously reported in the ASSURE and CheckMate 914 trials and report provocative findings regarding a molecule known as kidney injury molecule 1 or KIM-1, which is a type 1 membrane glycoprotein that has been identified as a minimally invasive potential peripheral blood circulating biomarker. The KIM-1 level of 86 pg/ml was identified as the optimized threshold for defining post-nephrectomy KIM-1 high vs KIM-1 low subgroups in the IMmotion010 trial. KIM-1 levels were measured at baseline or pre-treatment, at cycle 4 day 1, and at disease recurrence or discontinuation without disease recurrence. Baseline characteristics were balanced between the KIM-1 high and KIM-1 low groups, except perhaps for a slightly higher pathological stage in the KIM-1 high subgroup. I would like to highlight 3 key takeaways from this abstract. First, KIM-1 high level was associated with significantly worse DFS with a hazard ratio of 1.75. Second, patients in the KIM-1 high subgroup receiving atezolizumab had a 28% reduction in the risk of recurrence or death compared to those receiving placebo, while those in the KIM-1 low subgroup had comparable outcomes across both treatment arms. Third, patients in the KIM-1 high subgroup receiving atezolizumab were significantly less likely to experience an on-treatment increase in KIM-1 levels, which was associated with worse DFS in both high and low KIM-1 subgroups, regardless of treatment arm. Thus, these findings support the use of KIM-1 as both a predictive and prognostic biomarker in patients with RCC. Dr. Neeraj Agarwal: Yes, Rana, this is amazing data! I would like to add that these results warrant larger and, ideally, prospective studies to validate the utility of KIM-1 as a noninvasive biomarker for identifying minimal residual disease after nephrectomy and for predicting outcomes to immune checkpoint inhibitors. Dr. Rana McKay: Also, in the field of biomarkers, 2 abstracts interrogating different biomarkers in a different setting, so in patients with advanced or metastatic RCC were presented. Neeraj, could you tell us more about these abstracts? Dr. Neeraj Agarwal: Of course! I think you are referring to Abstracts 4504 and 4505. In abstract 4504, Dr. Toni Choueiri and colleagues sought to assess the clinical implications of different biomarkers in the CLEAR trial, which was a randomized phase 3 trial that led to the approval of the combination of pembrolizumab plus lenvatinib in the first-line mRCC setting. On the other hand, in abstract 4505, Dr. Brian Rini presented biomarker results in KEYNOTE-426, which was also a randomized phase 3 trial based on which the combination of pembrolizumab plus axitinib was approved in patients with mRCC. The authors in both trials sought to investigate the role of biomarkers in predicting treatment outcomes from 3 different angles. Starting with PD-L1 expression, the superiority of the combination arms over sunitinib was not impacted by PD-L1 status in both trials. Moving on to RCC driver gene mutations on whole exome sequencing, such as VHL, SETD2, PBRM1, and BAP1, ICI combination therapies improved outcomes regardless of mutation gene status, and this improvement was statistically significant with PBRM1 mutations in KEYNOTE-426 compared to wild-type PBRM1, but this did not replicate in the CLEAR trial. Finally, using transcriptomic signatures derived from RCC trials, especially the IMmotion 151 and JAVELIN Renal 101 trials, where 7 clusters or molecular subtypes were identified, the combination arms outperformed sunitinib in all clusters in both trials and the magnitude of this benefit differed across clusters. Dr. Rana McKay: Thank you for this very interesting summary and comparison of the results of these 2 abstracts. These findings support the use of ICI-based combinations in all patients with mRCC as a first-line option. Although these abstracts could not identify specific biomarkers that could guide us clinicians in treatment selection, they provide very interesting biological insights on these molecular biomarkers that are, however, not yet clinically actionable. Dr. Neeraj Agarwal: Very interesting point, Rana. Moving on to prostate cancer, let's start with abstract LBA5000 titled, “Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: The CHAARTED2 trial of the ECOG-ACRIN Cancer Research Group (EA8153).” Rana, what is your takeaway on this abstract? Dr. Rana McKay: As a reminder to our audience, the CHAARTED2 trial was a randomized open-label phase 2 study that compared the combination of cabazitaxel and abiraterone to abiraterone alone in patients with mCRPC previously treated with ADT plus docetaxel in the hormone-sensitive setting. The primary endpoint was progression-free survival. After a median follow-up of 47.3 months, Dr. Christos Kyriakopoulos and colleagues reported in LBA5000 that patients receiving the combination of cabazitaxel plus abiraterone had a 27% reduction in the risk of progression or death. However, there was no significant difference in overall survival between the two arms, with a median OS of 25 months in the cabazitaxel+abiraterone arm and 26.9 months in the abiraterone arm, although the study was underpowered for this endpoint. Regarding the toxicity profile, the combination of cabazitaxel and abiraterone was overall well tolerated with more cytopenias, as expected. Dr. Neeraj Agarwal: Very nice summary of this abstract, Rana. I would like to add that the treatment landscape of patients with mHSPC has evolved since the design of the study and now includes combination therapies of ADT + ARPI with or without docetaxel, and ADT + docetaxel is no longer a standard of care, which limits the applicability of these results in clinical practice today. Dr. Rana McKay: Excellent point, Neeraj. Let's discuss Abstract 5001, titled “CYCLONE 2: A phase 3 study of abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer”. Dr. Neeraj Agarwal: Sure! In the abstract featured at ASCO24, Dr. Matthew Smith and colleagues report the primary results of the CYCLONE 2 trial, which was a randomized phase 2/3 study that investigated the combination of abemaciclib plus abiraterone versus abiraterone monotherapy in patients with mCRPC. Stratification factors included radiographic progression at study entry, presence of measurable disease, and prior docetaxel for mHSPC. Part 1 of the study established the recommended phase 2 dose of abemaciclib at 200 mg twice daily. In part 2, patients were randomized to placebo or abemaciclib, and an adaptive interim analysis using prespecified criteria was performed and recommended the expansion of the study to part 3. The primary endpoint was investigator-assessed radiographic progression-free survival by RECIST 1.1 and PCWG3 criteria in the intention-to-treat population. At the time of the primary analysis, adding abemaciclib to abiraterone did not improve rPFS, with a hazard ratio of 0.83. The median rPFS was 22 months for the combination arm and 20.3 months for the abiraterone arm. The combination was well tolerated, and the safety profile was consistent with the known adverse events. Dr. Rana McKay: So, the addition of abemaciclib to abiraterone did not improve outcomes in patients with mCRPC. These findings suggest that no further investigation is warranted for abemaciclib or CDK4/6 inhibitors in biomarker-unselected patients with prostate cancer. Dr. Neeraj Agarwal: Rana, what's your take-home message on Abstract 5006, titled “Health-related quality of life results from PRESTO (AFT-19), a phase 3 randomized trial of intensification of androgen blockade in patients with high-risk biochemically relapsed castration sensitive prostate cancer”? Dr. Rana McKay: So, as a reminder to our audience, the PRESTO trial was a randomized phase 3 study that assessed the effects of intensified androgen receptor blockade in patients with biochemically recurrent prostate cancer following local therapies. Patients with a PSA doubling time of less than 9 months and no evidence of metastatic disease were randomized to receive either 52 weeks of ADT alone, ADT plus apalutamide, or ADT plus apalutamide plus abiraterone. In their paper published earlier this year in the Journal of Clinical Oncology, the authors showed that patients receiving ADT plus apalutamide with or without abiraterone had significantly longer PSA-progression-free survival than those receiving ADT alone. In the oral presentation featured at ASCO24, Dr. Ronald Chen and colleagues report health-related quality of life outcomes that were assessed using various questionnaires or scales at baseline, at cycle 7, which is around 6 months on treatment, and at the end of treatment. Results showed that this intensified approach with apalutamide did not significantly increase severe adverse events, did not lengthen the time to testosterone recovery, and did not meaningfully increase common treatment-related symptoms such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue. Importantly, additional intensification with abiraterone did not further improve PSA-PFS but did increase the rate of serious adverse events, lengthened the time to testosterone recovery, and increased hot flash interference. Dr. Neeraj Agarwal: So, in conclusion, the PRESTO trial supports using intensified androgen blockade with apalutamide to improve PSA-PFS in patients with high-risk biochemically recurrent prostate cancer without compromising health-related quality of life. However, adding abiraterone did not offer additional benefits and increased side effects. Dr. Rana McKay: Let's move on to LBA5002 titled, “A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.” Would you like to share your insights on this abstract with our listeners? Dr. Neeraj Agarwal: Absolutely. MAST was a randomized, double-blinded, placebo-controlled trial that investigated the impact of metformin on the progression of low-risk localized prostate cancer in patients choosing to undergo active surveillance. Eligible patients had biopsy-proven, low-risk, localized prostate cancer diagnosed within the past 6 months, characterized by a Gleason score of less than 6 observed in less than one-third of the total cores, less than 50% positivity in any one core, a PSA level of less than 10 ng/ml, and a clinical-stage between T1c and T2a. Patients were randomized in a 1:1 ratio to receive either metformin 850 mg twice daily or placebo for three years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint was time to progression, defined as the earliest occurrence of primary prostate cancer therapy, such as prostatectomy, radiation, hormonal therapy, or pathological progression on subsequent biopsies, which was defined as more than 1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher. The study included 407 patients, with 204 receiving metformin and 203 receiving a placebo. Results presented by Dr. Anthony Joshua showed no statistically significant difference in progression-free survival, including therapeutic and pathologic progression, with an unadjusted hazard ratio of 1.08. Interestingly, there was a signal that patients with a BMI more than 30 had a detriment to taking metformin with a higher risk of progression compared to those receiving placebo with an unadjusted HR of 2.39 and a p-value of 0.01. Dr. Rana McKay: I would like to add that this study showed that metformin use does not prevent the progression of low-risk localized prostate cancer on active surveillance and could represent a potential detriment for patients with high BMI at study entry. Dr. Neeraj Agarwal: Yes, Rana, I concur. Any final remarks before we conclude today's podcast? Dr. Rana McKay: Thank you, Neeraj; it's been wonderful being here with you today and you having me on the podcast to highlight these important advances and the amazing work that many investigators are conducting and the patients who were involved in the context of these trials. It's really excellent to see these updated results. Dr. Neeraj Agarwal: Before we wrap up this podcast, I would like to say that we have reviewed a selection of abstracts addressing prostate, bladder, and kidney cancer, which are significantly impacting our medical practices now and in the near future. Rana, thank you for sharing your insights today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion. Many thanks. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Find out more about today's speakers: Dr. Neeraj Agarwal  @neerajaiims  Dr. Rana McKay @DrRanaMcKay   Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:      Dr. Neeraj Agarwal:       Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas   Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus

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Key Abstracts in GU Cancers at ASCO24

Play Episode Listen Later May 25, 2024 26:04

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Jeanny, it's great to have you on the podcast. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here. Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.” Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma. In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response. Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone. The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone. Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients. In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, as quick reminder to our audience, this regimen was tested in the EV-302 phase 3 trial, where patients with previously untreated, locally advanced or metastatic urothelial carcinoma were randomized to receive enfortumab vedotin, plus pembrolizumab or gemcitabine plus either cisplatin or carboplatin. These data were also first presented at ESMO 2023 and subsequently published in the New England Journal of Medicine. They showed that this immune based combination significantly improved both progression free survival and overall survival, which were the primary endpoints compared to chemotherapy. In this abstract, Dr. Shilpa Gupta from the Cleveland Clinic and colleagues present the results of patient reported outcomes based on quality-of-life questionnaires in this trial. Time to pain progression and time to confirm deterioration were numerically longer in patients treated with EV plus pembro, and patients with moderate to severe pain at baseline receiving this combination had a meaningful improvement in the Brief Pain Inventory Short-Form worst pain from week 3 through 26. Dr. Neeraj Agarwal: Thank you, Jeanny. This means that patients treated with EV plus pembro did not only have improved survival compared with platinum-based chemotherapy, but also improvement in their quality-of-life and functioning, further supporting the value of this combination for patients with locally advanced or metastatic urothelial carcinoma. This is terrific news for all of our patients. Before we wrap up the bladder cancer section, would you like to tell our listeners about Abstract 4565, which provides the data on the efficacy of trastuzumab deruxtecan in patients with bladder cancer? Dr. Jeanny Aragon-Ching: Yes, Neeraj; this is timely given the recent FDA approval, which we will talk about. The abstract is titled, “Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2 Expressing Solid Tumors: Results from the Bladder Cohort of the DESTINY-PanTumor02 Study.” And as a quick reminder, the DESTINY-PanTumor02 was a phase 2 open-label study where trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 expression on cancer cells, was evaluated in patients with HER2-expressing locally advanced or metastatic disease who previously received systemic treatment or who had no other treatment options. The expression of HER2 was evaluated on immunohistochemistry by local or central testing. The primary endpoint was confirmed objective response rate by investigator assessment. Secondary endpoints included duration of response, progression free survival, disease control rate, and safety. The primary analysis, which was published in the Journal of Clinical Oncology, showed an ORR of 37.1% and responses across all cohorts and the median duration of response was 11.3 months. Based on these results, fam-trastuzumab deruxtecan-nxki was just granted accelerated FDA approval for unresectable or metastatic HER2-positive solid tumors in April 2024. So, back to this abstract; Dr. Wysocki and colleagues report the results of the bladder cancer cohort. This study included 41 patients with urothelial cancer and at a median follow up of around 12.6 months, the objective response rate among these patients was 39%, the median PFS was 7 months, and the duration of response median was 8.7 months. The disease control rate at 12 weeks was around 71%. Regarding the safety profile, 41.5% of patients experienced grade ≥3 drug related adverse events and interstitial lung disease or pneumonitis did occur in about 4 patients. Although there was no statistical comparison between different groups, the ORR was numerically highest among the HER2 3+ group with 56.3%. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data support consideration of trastuzumab deruxtecan as a salvage therapy option for pre-treated patients with HER2 expressing urothelial cancers and show that we are extending our treatment options to include therapies with novel mechanisms of action. This is definitely exciting news for patients with bladder cancer. Dr. Jeanny Aragon-Ching: Yes, absolutely, Neeraj. Now, let's switch gears a bit to prostate cancer. Could you tell us about Abstract 5005 which is titled, “EMBARK Post Hoc Analysis of Impact of Treatment Suspension on Health Quality-of-Life?” Dr. Neeraj Agarwal: Of course, I'd be happy to. So, enzalutamide was recently granted FDA approval for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk of metastasis, based on the results of the EMBARK trial, which was a phase 3 study where patients with high-risk biochemical recurrence were randomized to receive either enzalutamide with leuprolide, enzalutamide monotherapy, or placebo plus leuprolide. The primary endpoint was metastasis-free survival with secondary endpoints including overall survival and safety. Results showed that patients receiving enzalutamide alone or enzalutamide plus leuprolide had significantly improved metastasis-free survival compared to those treated with leuprolide alone while preserving health-related quality-of-life. One important aspect in the design of the trial was that patients who achieved undetectable PSA at week 37 underwent treatment suspension. The treatment was resumed if PSA rose to more than 2 ng/ml for patients who underwent radical proctectomy or when PSA rose to more than 5 ng/ml for those who did not undergo surgery. In this abstract, Dr. Stephen Freedland and colleagues present a post-hoc analysis of health-related quality-of-life outcomes after treatment suspension between weeks 37 and 205. They found that treatment was suspended in 90.9% of patients receiving enzalutamide plus leuprolide, 85.9% of those receiving enzalutamide monotherapy, and 67.8% of those receiving leuprolide monotherapy. Among those patients who stayed on treatment suspension, a trend toward numerical improvement in health-related quality-of-life after week 37 was seen in all 3 arms and this reached clinically meaningful threshold at week 205 in pain questionnaires, physical well-being, urinary and bowel symptoms. For hormonal treatment side effects, all arms reached clinically meaningful improvement at the subsequent assessments of week 49 to week 97. However, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 in patients receiving the combination of enzalutamide and leuprolide and those treated with leuprolide. Concerning sexual activity, a clinically meaningful improvement was reported only in patients receiving enzalutamide plus leuprolide, possibly because sexual function was better preserved prior to suspension in the enzalutamide monotherapy arm and thus there was less opportunity for “improvement” while on suspension. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for this great summary. This analysis confirms that treatment suspension in good responders might lead to a clinically meaningful improvements in health-related quality-of-life. Now, moving on to patients with metastatic castration-resistant prostate cancer, what can you tell us, about Abstract 5008 titled, “Baseline ctDNA analyses and associations with outcomes in taxane-naive patients with mCRPC treated with 177Lu-PSMA-617 versus change of ARPI in PSMAfore”? Dr. Neeraj Agarwal: Sure, Jeanny. The PSMAfore trial was a phase 3 study that compared the efficacy of 177Lu-PSMA-617 versus an ARPI switch in patients with mCRPC and prior progression on a first ARPI, and not previously exposed to docetaxel chemotherapy. The primary endpoint was rPFS and OS was an important secondary endpoint. The primary analysis presented at ESMO 2023 showed a significantly prolonged rPFS in patients receiving lutetium. In the abstract that will be featured at the 2024 ASCO Annual Meeting, Dr. Johann De Bono and colleagues present an exploratory analysis regarding the associations between baseline circulating tumor DNA and outcomes. ctDNA fraction was evaluated in all samples as well as alterations in key prostate cancer drivers prevalent in more than 10% of participants. The investigators sought to interrogate the association of ctDNA fraction or alterations with rPFS, PSA response, and RECIST response at data cutoff. They showed that median rPFS was significantly shorter in patients with a ctDNA fraction >1% compared to those with a fraction < 1% regardless of the treatment arm. Furthermore, ctDNA fraction >1% was also associated with worst RECIST response and PSA50 response. Regarding prostate cancer drivers, median rPFS was significantly shorter in patients with alterations in the AR, TP53 or PTEN in both treatment arms. There was no significant association between ctDNA alterations and PSA or objective responses. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that the presence of a ctDNA fraction >1% or alterations in AR, P53 and PTEN were all associated with worse outcomes regardless of treatment with lutetium or change in the ARPI. These data are definitely important for counseling and prognostication of patients in the clinic and may guide the design of future clinical trials. Let's move on to kidney cancer. Neeraj, do you have any updates for us? Dr. Neeraj Agarwal: Sure. In Abstract 4512 titled, “A Multi-institution Analysis of Outcomes with First-Line Therapy for 99 Patients with Metastatic Chromophobe Renal Cell Carcinoma,” Dr. Sahil Doshi and colleagues present a retrospective, multi-institutional study comparing survival outcomes, including time-to-treatment failure and overall survival, between different first-line treatment options in patients with metastatic chromophobe renal cell carcinoma, where limited clinical trial data exists to guide systemic therapy. They categorized patients into 4 treatment groups: and immune checkpoint inhibitors + targeted therapy doublets (such as ICI VEGF TKI); pure immune checkpoint inhibitor monotherapy and doublets (such as ipilimumab plus nivolumab); targeted therapy doublets (such as lenvatinib plus everolimus), and targeted monotherapy (such as sunitinib). They identified 99 patients, of whom 54 patients received targeted monotherapy, 17 received ICI VEGF-TKI, 14 received targeted doublet, and 14 patients received only ICI therapies. So the patients treated with any doublet containing a targeted agent had a 52% decrease in the risk of treatment failure and a 44% decrease in the risk of death compared to those treated with targeted monotherapy. The median time to treatment failure was 15 months with IO-targeted doublet, and the median overall survival was 56 months. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that targeted doublet regimens resulted in a longer time to treatment failure and overall survival compared to any monotherapy in patients with chromophobe metastatic RCC and definitely provides valuable insights on treatment selection, albeit I would say there's still a small number of patients that were included in this retrospective analysis. Dr. Neeraj Agarwal: I completely agree this is a relatively small number of patients, but I decided to highlight the abstract given how rare the cancer is, and it is highly unlikely that we'll see large randomized clinical trials in patients with metastatic chromophobe renal cell carcinoma. So, before we wrap up the podcast, what would you like to tell us about Abstract 5009 which is titled, “A Phase II Trial of Pembrolizumab Platinum Based Chemotherapy as First Line Systemic Therapy in Advanced Penile Cancer: HERCULES (LACOG 0218) Trial.” Dr. Jeanny Aragon-Ching: I'm glad you brought this up, Neeraj. As our listeners may know, advanced penile squamous cell carcinoma has a poor prognosis with limited treatment options. From this perspective, the results of the LACOG 0218 trial are very important. As you mentioned, this was a phase 2 single-arm study evaluating the addition of pembrolizumab to platinum-based chemotherapy as first-line treatment in patients with metastatic or locally advanced penile squamous cell carcinoma not amenable to curative therapy. Patients enrolled received chemotherapy, namely 5-Fluorouracil with cisplatin or carboplatin and pembrolizumab 200 mg IV every 3 weeks for 6 cycles, followed by pembrolizumab 200 mg IV every 3 weeks up to 34 cycles. The primary endpoint was confirmed overall response rate by investigator assessment. In the 33 patients eligible for the efficacy analysis, the confirmed ORR by investigator assessment was 39.4% and included one complete response and 12 partial responses. The confirmed ORR was 75% in patients with high TMB and 55.6% in patients positive for HPV16, making TMB and HPV16 potential predictive biomarkers for efficacy in this study. Concerning the toxicity profile, any grade treatment-related adverse events were reported in around 92% of patients, and grade 3 or more treatment-related adverse events occurred in 51% of patients. 10.8% of patients discontinued treatment due to adverse events. Dr. Neeraj Agarwal: Thank you, Jeanny. I would like to add that HERCULES is the first trial to demonstrate the efficacy of an immune checkpoint inhibitor in advanced penile squamous cell carcinoma with a manageable safety profile. Thus, the combination of ICI with platinum-based chemotherapy is a promising treatment for advanced penile squamous cell carcinoma and warrants further investigation. Dr. Jeanny Aragon-Ching: I agree, Neeraj. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Jeanny, I really want to thank you for your participation and valuable insights. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. It was a pleasure. Dr. Neeraj Agarwal: As we bring this podcast to an end, I would like to acknowledge the significant advances happening in the treatment of patients with genitourinary cancers. During our upcoming 2024 ASCO Annual Meeting, there will be an array of different studies featuring practice-changing data presented by researchers and physicians from around the globe. I urge our listeners to not only participate in this event to celebrate these achievements, but to also play a role in sharing these cutting-edge data with healthcare professionals worldwide. Through our collective efforts, we can surely optimize the benefits of patients on a global scale. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you very much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.

university time speaker dna medicine cancer safety impact trial patients journal os fda iv results pfizer analysis psa ev outcomes gu embark io astrazeneca secondary hercules bayer abstract oncology merck ici efficacy cleveland clinic prostate cancer janssen checkmate new england journal novartis agarwal sanofi precision medicine asco genentech amgen orr bristol myers squibb takeda characterization rcc her2 pfs clinical oncology nektar abstracts tmb wysocki esmo eisai asco annual meeting nivolumab pten ctdna emd serono tp53 jeanny aveo foundation medicine p53 crispr therapeutics health quality medimmune arpi seattle genetics fluorouracil dendreon pharmacyclics janssen oncology transcript dr recist neeraj agarwal hpv16 mei pharma

What's New in Prostate Cancer, RCC, and mUC at GU24

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Jan 22, 2024 25:10

Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year. You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod. Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression. Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting. The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits. Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj? Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods. Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma. Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib. Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma. Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy. Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review. I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting. So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers. Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist. So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer. Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts. So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures:  Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.

university moving speaker study utah trial patients os phase fda consistent pfizer similar psa unite outcomes drs gu astrazeneca mri secondary atm bayer abstract oncology merck hu prostate cancer janssen checkmate novartis sanofi precision medicine asco genentech amgen itt bristol myers squibb takeda older men rcc brca1 pfs enrolled parp brca2 nektar abstracts crpc guha randomized trial hif eisai muc huntsman cancer institute nivolumab first line treatment emd serono jeanny aveo foundation medicine crispr therapeutics ipilimumab fgfr medimmune arpi asco gu seattle genetics everolimus sunitinib dendreon pharmacyclics janssen oncology transcript dr recist neeraj agarwal ccrcc mei pharma

Cancer Topics – Research to Practice: Prostate Cancer (Part 2)

Play Episode Listen Later Jul 19, 2023 31:09

In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. Part One involved a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. Today's scenario focuses on de novo metastatic prostate cancer. Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:13), going beyond the one-size-fits-all approach (4:54), and thinking about the patient as a whole (13:39). Speaker Disclosures Dr. Kriti Mittal: Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group Research Funding - Pfizer Dr. Jorge Garcia: Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology; Genentech/Roche; Lilly Other Relationship - FDA Resources ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Disclosures for this podcast are listed on the podcast page. Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today, we'll explore how we interpret and integrate recently reported clinical research into practice. In a previous episode, we explored the clinical scenario of localized prostate cancer progressing to metastatic hormone-sensitive disease. Today, our focus will be on de novo metastatic prostate cancer. My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist Chair and the current Chair of the Solid Tumor Oncology Division at University Hospitals Seidman Cancer Center. Here are the details of the patient case we will be exploring: The patient also notes intermittent difficulty in emptying his bladder with poor stream for the last six months. A CT scan of the abdomen and pelvis demonstrates enlarged prostate gland with bladder distension, pathologically enlarged internal and external iliac lymph nodes, and multiple osteolytic lesions in the lumbar sacral, spine, and pelvic bones. A CT chest also reveals supraclavicular lymphadenopathy and sclerotic foci in three ribs. So this patient meets the criteria for high-volume disease and also has axial and appendicular lesions. The patient was admitted for further evaluation. A bone scan confirmed uptake in multiple areas identified on the CT, and a PSA was found to be greater than 1500. Biopsy of a pelvic lymph node confirmed the diagnosis of prostate cancer. This patient is somewhat different from the first case we presented in terms of timing of presentation; this patient presents with de novo metastatic high-volume disease, in contrast to the first patient who then became metastatic after undergoing treatment for high-risk localized disease. Would you consider these two cases different for the purposes of dosing docetaxel therapy when you offer upfront triplet therapy combinations? Dr. Jorge Garcia: That's a great question. I actually do not. The natural history of someone with localized disease receiving local definitive therapy progressing over time is different than someone walking in with de novo metastatic disease. But now, with the challenges that we have seen with prostate cancer screening, maybe even COVID, to be honest with you, in North America, with the late care and access to testing, we do see quite a bit of patients actually walking in the office with de novo metastatic disease. So, to me, what defines the need for this patient to get chemotherapy is the volume of his disease, the symptoms of his disease – to be honest with you – and the fact that, number one, he is clinically impaired. He has symptomatic disease, and he does have a fair amount of disease, even though he may not have visceral metastasis. Then his diseases give him significant pain. Oral agents are very good for pain control. I'm not disputing the fact that that is something that actually these agents can do. But I also believe I'm senior enough and old enough to remember that chemotherapy, when it works, can actually really alleviate pain quite drastically. So for me, I think that the way that I would probably counsel this patient is to say, "Listen, we can give you ADT plus an oral agent, but I really believe your symptomatic progression really talks about the importance of rapid control of your disease.” And based upon the charted data from the United States, and equally important, PEACE-1, which is the French version of ADT, followed by abiraterone, if you will, and certainly ARASENS is the standard of care for me for a patient like this will be triple therapy with ADT and docetaxel. What I think is important for us to remember is that, in ARASENS, it was triple therapy together. I am worried sometimes about the fatigue that patients can have during the first six cycles of docetaxel. So oftentimes, I tell them if they're super fit, I may just do triple therapy up front, but if they I think they're going to struggle, what I tell them is, "Hey, we're going to put you on ADT chemotherapy. Right after you're about to complete chemo, we'll actually add on the darolutamide." So I do it in a sequence, and I think that's part of the data; we just still don't know if it should be given three at front or ADT chemo, followed by immediately, followed by an ARI. So I love to hear if that's how you practice or you perhaps have a different thought process. Dr. Kriti Mittal: So I usually start the process of prior authorization for darolutamide the day I meet them for the first time. I think getting access to giving docetaxel at the infusion center is usually much faster than the few weeks it takes for the prior authorization team to get copay assistance for darolutamide. So, in general, most of my patients start that darolutamide either with cycle two or, depending on their frailty, I do tend to start a few cycles in like you suggested. I've had a few patients that I've used the layered-in approach, completing six cycles of chemotherapy first and then layering in with darolutamide. I think conceptually the role of intensifying treatment with an androgen receptor inhibitor is not just to get a response. We know ADT will get us a PSA response. I think the role of an androgen receptor inhibitor is to prevent the development of resistance. So, delaying the development of resistance will be pertinent to whether we started with cycle one, cycle six, or after. So, we really have to make decisions looking at the patient in front of us, looking at their ECOG performance status, their comorbidities, and frailty, and we cannot use a one-size-fits-all approach. Dr. Jorge Garcia: Yeah, I like that and I concur with that. Thank you for that discussion. I think that you may recall some of our discussions in different venues. When I counsel patients, I tell the patients that really the goal of their care is on the concept of the three Ps, P as in Peter. The first P is we want to prolong your life. That's the hallmark of this regimen, the hallmark of the data that we have. That's the goal, the primary goal of these three indications is survival improvement. So we want to prolong your life so you don't die anytime soon from prostate cancer. The second P, as in Peter, is to prevent, and the question is preventing what? We want to prevent your cancer from growing, from growing clinically, from growing radiographically, and from growing serologically, which is PSA and blood work. Now, you and I know and the audience probably realize that the natural history of prostate cancer is such that traditionally your PSA will rise first. There is a lead time bias between the rise and the scan changes and another gap in time between scans and symptoms. So it's often not the case when we see symptomatic disease preceding scans or PSAs, but sometimes in this case, it's at the same time. So that is the number one. And as you indicated, it's prevention of resistance as well, which obviously we can delay rPFS, which is a composite endpoint of radiographic progression, symptomatic progression, and death of any cause. But the third P is I called it the P and M, which is protecting and maintaining, and that is we want to protect your quality of life while we treat you. And we want to maintain your quality of life while we treat you. So to me, it's critically important that in addition of aiming for an efficacy endpoint, we don't lose sight of the importance of quality of life and the protection of that patient in front of us. Because, undoubtedly, where you get chemo or where you get an oral agent, anything that we offer our patients has the potential of causing harm. And I think it is a balance between that benefit and side effect profile that is so critically important for us to elucidate and review with the patient. And as you know, with the charted data, Dr. Alicia Morgans now at Dana-Farber, published a very elegant paper in JCO looking at the impact of docetaxel-based chemotherapy as part of the charted data in the North American trial and into quality of life. And we clearly define that your quality of life may go down a bit in the first few months of therapy, predictably because you're getting chemotherapy. But at the end of the six months, nine months, and certainly at the end of a year mark, the quality of life data for those who receive ADT and chemotherapy was far better than those who actually got ADT alone. Now, if you look at the quality of data for RSNs, a similar pattern will appear that although chemotherapy is tied to misconceptions of significant toxicity, in our hands, in good hands, and I think our community of oncology in North America are pretty familiar with the side effects and how to manage and minimize side effects on chemotherapy, I think it still requires a balance and a thoughtful discussion to make sure that we're not moving forward chasing a PSA reduction at the expense of the quality of life of the patient. So I think orchestrating that together with the patient as a team is critically important as well. Dr. Kriti Mittal: Thank you, Dr. Garcia. Moving on to the next concept we'd like to discuss in today's podcast the role of PARP inhibitors. Case Two was treated with androgen deprivation docetaxel and darolutamide. Consistent with current guidelines, the patient was also referred to germline testing and was found to be BRCA 2-positive. The patient's disease remained stable for 24 months, at which time he demonstrated disease progression, radiographically and clinically, and his disease was termed castration-resistant. There has been a lot published in the last few years regarding the role of PARP inhibitors in metastatic castration-resistant prostate cancer, or mCRPC. The PROfound trial led to the approval of olaparib in patients with deleterious mutations in HRR genes for those who had been treated previously with AR-directed therapy. The TRITON2 trial led to the approval of rucaparib in the same month for mCRPC patients with BRCA mutation for those patients who had previously been treated with AR inhibitors and taxine-based chemotherapy. More recently, we saw data from the TRITON3 trial exploring the role of rucaparib versus physicians' choice of docetaxel versus AR-inhibitor therapy in the mCRPC space for patients harboring BRCA 1, BRCA 2, or ATM mutation. Based on these data, it would be very tempting to offer a PARP inhibitor to the patient in case two. While regulatory authorities are still reviewing those data for approval, how would you consider treating this newly castrate-resistant patient in the frontline setting? Would you consider a PARP inhibitor in the frontline treatment of mCRPC in this patient with a BRCA 2 mutation? Dr. Jorge Garcia: So that's a loaded question, to be honest with you. We have compelling data, but controversial data, as you know as well. So I think that since we have a genomic profile on this patient and we know he had high volume disease, then the first thought to me is not a genetic or a genomic question or a sequence. It's actually a clinical question, to be honest with you. And that is: How are you progressing? Because I think that if you're progressing serologically, you and I may think of that patient differently. If you're progressing radiographically with alone plus minus PSA production but no symptoms, you may also tilt your scale into this life-prolonging agents in a different way. Whereas if you have true symptomatic disease, knowing what you know, prior therapy, CrPC with a BRCA 2 alteration, then you may actually go for something different. So if it's a rising PSA, if it is radiographic, but the patient is stable clinically, is not basically compromised by symptomatic disease, I do feel that a PARP inhibitor as a single agent would be a very reasonable choice. In this case, you can use, obviously, rucaparib. You can use olaparib. I don't have a vested interest in either/or. I think either/or is fine. The subtleties and side effects, as you know, the olaparib data was probably the data that you and I probably are more accustomed to, used to the most just by virtue of how the agents got registered in the United States. But either/or, I think a PARP inhibitor would be a reasonable approach. I think the question perhaps, and I pitch that back to you, is what are you looking for with a PARP inhibitor? Because, as you know, all DNA repair deficiencies are not biologically the same. They do not respond the same way to PARP inhibitors. And even BRCA 2, where we think it's monoallelic or biallelic, may have subtleties in how those patients respond to PARP therapy. But the answer is yes, obviously, you have a biomarker, the patient has it, you can use it. I think the question is, how are you going to follow the patient? And what is going to be the endpoint that you're going to pay attention to in this case to find that the patient has a benefit or not granted, that could be PSA driven, but I think that perhaps I'm pushing you to think beyond PSA. Dr. Kriti Mittal: I agree, Dr. Garcia. I think we need to think about the patient as a whole. PSA-based changes in treatment are not generally part of our practice. I think evaluating the patient for symptoms and also thinking about the sites of progression, sites of disease they've had in the past, preventing development of cord compression, because some of these patients progress very rapidly and present with cord compression at the time of progression. Those are the things we are trying to predict and prevent. I think in a patient with BRCA 2 mutation, in this situation, I would feel compelled to offer rucaparib, given that even in the intention-to-treat analysis, the hazard ratio was 0.6 in terms of median progression-free survival. I think what was quite impressive was the subset analysis comparing rucaparib versus docetaxel. And that was something surprising. And I think we'll have to wait for long-term outcomes. But certainly, for a BRACA 2-mutated patient, this could be a reasonable consideration provided the drug is available and approved. Dr. Jorge Garcia: As you know, the three most common DNA repair deficiencies that we see are BRCA1, BRCA2, and ATM. BRCA2 is probably the one that we see the most. But we also recognize that with the limited data we have for ATMs, that patients with an ATM abnormality do not tend to benefit the most. And then yet we have also another series of DNA repair deficiencies, deficiencies, PALB2, CHEK2, CDK12 and so forth. And yet we have some exquisite responses to some of those patients. So I can tell you that I have a patient of mine who had an ATM mutation, a germline ATM mutation, and I predicted that initially that the likelihood of benefit to a PARP inhibitor would be low. He was placed on a PARP inhibitor and surprise, surprise, he was on a PARP inhibitor for almost a couple of years. What I want to convey to the audience is that if you have the appropriate biomarker, you certainly should consider a PARP inhibitor in this scenario. I think the bigger question is also understanding that not every DNA repair would benefit the same way. So being very thoughtful and very structured as to how you're going to manage the patient, it cannot be PSA only, the patient has to be followed radiographically and clinically because I would argue that if this patient had just a serologic progression, I would put the patient on a PARP inhibitor and the PSA kinetics change north, but slowly, what is the urgency of you switching the patient to something else? And also the misconception that if you look at PROfound, that olaparib for that matter has to always be given after docetaxel. That's not the case. The makeup of PROfound is different than this patient, obviously, because this patient got triple therapy upfront, whereas most patients on the PROfound were CRPC who receive chemotherapy in the CRPC space. But yet undoubtedly, I think that your case illustrates the importance of next-generation sequencing and the importance of understanding the access to two oral PARP inhibitors that are super solid. I think that perhaps the bigger question is going to be should you do a PARP inhibitor alone or should we use a combination of a PARP inhibitor plus an oral agent, such as in this case, maybe abiraterone acetate plus olaparib. Or maybe even thinking of TALAPRO, maybe enza plus a PARP inhibitor. So I don't know where you sit on those thoughts, Doctor-. Dr. Kriti Mittal: I change toxicity considerations, temper my enthusiasm for offering PARP inhibitors in combination with AR inhibitors or abiraterone at this time. I think I would certainly consider monotherapy with rucaparib for a patient in this situation. I am not entirely convinced that putting a patient through dual treatment in the mCRPC setting in the frontline, I don't think we are there yet. Dr. Jorge Garcia: There are two very important trials that are looking at the combination of an adrenal biosynthesis inhibitor plus olaparib in this context, and one is PROpel and the other one is MAGNITUDE. And both trials have very different results in many ways because they look at patients with a biomarker, meaning DNA repair, and patients without the biomarker. And I think the bigger question is, should this patient who was an abiraterone– Let's say this patient hypothetically was on a PEACE-1-like style. So the patient got ADT or triple therapy but was an abiraterone or an adrenal biosynthesis inhibitor instead of chemotherapy. And the patient was progressing slowly on abiraterone, you knew that the patient had a DNA repair deficiency. How comfortable with the PROpel and MAGNITUDE data would you and I feel to add on or layer, if you allow me to express it like that, a PARP inhibitor into this regime? Dr. Kriti Mittal: My personal interpretation of the currently available data is that at this point, combination therapy is not something I would use in my clinical practice. I think there are two camps in the GU oncology community of how people interpret the PROpel, MAGNITUDE, TRITON, and TALAPRO data in full. I think each of these trials had very different patient populations. I think in a biomarker unselected population, I would certainly not advocate for combination therapy. But even in the biomarker-selected population, I think how the biomarkers were tested and how the populations were defined may not always match what we are doing in clinical practice. And so I would, at this time, advocate for monotherapy over combination therapy. Dr. Jorge Garcia: I'm sure the audience will have probably read or heard about PROpel and MAGNITUDE and the data in patients without a biomarker positivity disease. So I'd love to hear your thoughts as to if you had no biomarker. By that I mean if you had a patient with CRPC, with metastatic CRPC without a DNA repair deficiency, would you consider using an adrenal biosynthesis inhibitor and a PARP inhibitor together based upon the potential synergistic of additive benefits and some of the data to suggest that you can delay rPFS when you combine therapy, but in the absence of biomarker positivity. Dr. Kriti Mittal: In the absence of biomarker positivity, I think the preclinical data are stronger than the clinical results we are seeing in trials. So while I think we should continue researching further into this because there certainly is preclinical rationale, looking at the clinical outcomes from these several trials, I would not offer PARP inhibitor to an unselected patient. Dr. Jorge Garcia: Great. Dr. Kriti Mittal: Moving on to second-line treatment for castration-resistant prostate cancer. I think talking of access issues and talking about the current treatment paradigms in the United States, there is still not widespread availability of lutetium. The listeners would love to hear your thoughts, Dr. Garcia, on practical management tips, safety issues, and the multidisciplinary nature of the management of lutetium therapy. Dr. Kriti Mittal: So I think the challenges with lutetium are multiple. Number one is the correct identification of the patient, the ideal patient for lutetium. Secondly is who manages the patient and as you indicated, the importance of a team approach in that. Thirdly is how do we follow that patient during therapy? So it's beyond the technical aspects of who infuses the patient. Fourthly is what are the true goals of lutetium for that patient population and the side effects that those patients may embark on that some people may not be fully aware of and creates complexity. And lastly, perhaps, is how the movement, how we develop lutetium in CRPC and how we're going to move lutetium or have started to move lutetium and alike, meaning radiopharmaceuticals, radioligand-based therapies outside lutetium opinion and others as you know, earlier into the natural history of prostate cancer, maybe even in the locally advanced disease in combination with radiation or for patients with N1 positive disease. So it's a lot of movement in that space. I think that this is just the beginning of radiopharmaceutical entering diagnostics. But let me just address this succinctly, if I may. Number one, you do need a PET PSMA in order for you to select the patient because we're talking about a potential biomarker. But this is what I call an imaging biomarker. If you see it, you treat it. So the standard of care right now for lutetium is very simple: you need to have men with metastatic castration-resistant prostate cancer. Two, you need to have failed a prior oral agent, in this case, a novel hormonal agent, independent of which agent you have seen, independent of the timing when you have seen an oral agent at the front, the middle, the end. And lastly, you have to have progress through chemotherapy. Yet again, it depends on when you see chemo. So if you have someone who has high volume metastatic disease from the beginning, de novo disease, and you got ADT, daro, and docetaxel, and the patient progresses, that patient can go on. If that patient has a positive PSMA PET, that patient can go on to get lutetium. Similarly, if you have someone who got ADT alone in the adjuvant space for radiation therapy, progress, got an oral agent, progress, got a PARP or not, or got docetaxel, that patient could also be a candidate for lutetium. It's dependent on how you run the patient through therapy. Secondly is who gives lutetium? So I do believe, and I may be biased, I certainly believe in the importance of a team approach with radiation oncology and nuclear medicine. But the reality of it is, I believe these patients are so advanced in their stage of their disease, then the idea of quarterback, in my personal opinion, resides in medical oncology. And I think the bigger question is going to be if nuclear medicine at your given institution is going to be delivering lutetium, or is it going to be radiation oncology? And I think, as you know, in places in America, it's RadOnC, in other places is NucMed, in our institution right now it is NucMed. Having said that, I do predict that for those places where nuclear medicine is heavily involved in delivering lutetium or partnering with MedOnc to deliver lutetium, radiation oncology in the future will have a bigger role as well because we are moving lutetium earlier in settings where radiation oncology is commonly used, such as high-risk prostate cancer patients, or even in the salvage setting, or even in patients with metastatic disease, where we want to combine radiation and lutetium, which are part of clinical trials as we think through for the future. But either/or, I think the quarterback should be really MedOnc in this case. Thirdly is how do we do it? So clearly, at least in my practice, and I think it's probably standard across the United States, MedOnc will see the patient, determine viability and feasibility of therapy, determine who's the ideal candidate, discusses the pros and the cons, and then works along with RadOnc or NucMed to start the process. As you know, it is once every six weeks. So here in my practice, we will see the patient every time before treatment. Sometimes we see them the day off, sometimes we see them a few days before. Patients will get blood work. Specifically, we're interested in seeing everything CMPs, but certainly blood counts, red cell counts, platelets, and white cell counts, just to make sure that patients do not start with impaired bone marrow that can increase the risk for myelosuppression and therefore significant challenges with side effects, hematologic side effects, specifically. And we do that. Sometimes we see them, sometimes our nurse practitioners would do so. And then the patient will basically follow through and complete up to six cycles of treatments. Six times six, that's actually 36 weeks or so. That's a long time on therapy for those who can get six cycles. I think the question becomes how do you follow those patients? And if we pay attention to the VISION data, as you know, those patients were actually followed serially quite closely on trial every eight weeks for the first 24 weeks, and then they stretch the scans out. But the scans that we're using in the trial are conventional imaging. And I think the bigger question that you and I will have is if we get a PET PSMA to use to make that decision to get on lutetium PSMA, should I go back and use a CT or so to stage the patient? I think we're moving more toward PET follow-up, but we also don't know fully the impact of lutetium PSMA on PSMA metabolically during treatment. I think that we all recognize anecdotally and at least with some of the emerging data and we have the SUV may change, that PSA reductions also appear to be important as to define who is likely to benefit or not. But those are questions that remain to be seen, to be honest with you. We follow the patients serologically, clinically, and radiographically. And at least in my group, we tend to do PSMA PETs in between therapy to ascertain the impact of therapy in radiographic and also metabolic changes. And lastly is how we manage side effects. So I think that I'm pretty OCD about these patients because I have seen in my practice patients having outstanding responses to therapy but unfortunately become transfusion dependent, either transiently or permanently, just by virtue of side effects. And I think the importance of understanding the most common side effects of lutetium, in this case fatigue, myelosuppression, xerostomia, are really, really important. And that is the importance of having a multi-team effort approach so everybody is fully aware of the baseline characteristics of that patient or how the patient is enduring therapy and how the therapy is impacting the quality of life and impacting bone marrow production for those patients. I think I remind the audience that the vast majority of our patients do have bone metastases. In fact, in the VISION trial it was around what, over 85, 90% of patients are so with bone metastases. So their marrow has already been impacted not only by disease but equally importantly by the prior chemotherapy that they may have seen. And some of the patients that we have in the first bubble effect is they have seen probably docetaxel, some may even have seen dual therapy with cabazitaxel as a second-line chemotherapy. So I think the understanding as to how you manage the side effects is critically important for our patients as well. Dr. Kriti Mittal: Those are very relevant, practical life issues. Thank you Dr. Garcia for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. [28:54] The ASCO Education podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Dr. Jorge Garcia: Thank you, Kriti. It's great to see you and thanks again to ASCO for the amazing opportunity to be here with you guys today. I hope the audience can see the benefit of understanding how the many changes we have seen have impacted our patients in a positive way. So thank you again for the opportunity. Dr. Kriti Mittal: Thank you, Dr. Garcia, and thank you so much to the ASCO team for inviting me. This was a great experience. Thank you Dr. Garcia for sharing your perspective on incorporating recent research advances into the management of patients with de novo metastatic prostate cancer. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

THOR, CONTACT-03, and Other Advances in GU Cancers at ASCO23

Play Episode Listen Later Jun 27, 2023 23:25

Drs. Rana McKay and Jonathan Rosenberg highlight key advances in genitourinary cancers featured at the 2023 ASCO Annual Meeting, including the THOR study in mUCC, VESPER in muscle-invasive bladder cancer, CONTACT-03 in mRCC, and TALAPRO-2 in mCRPC. TRANSCRIPT Dr. Rana McKay: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Rana McKay, your guest host for the podcast today. I'm a GU medical oncologist at the Morris Cancer Center at the University of California in San Diego and an associate professor at the University of California in San Diego School of Medicine. Joining me today is Dr. Jonathan Rosenberg, the chief of the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center in New York. We'll be discussing practice-changing studies and other key advances in genitourinary cancers that were featured at the 2023 ASCO Annual Meeting. You'll find our full disclosures in the transcript of this episode, and disclosures of all guests featured on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod. Jonathan, it's great to have you with us today. How are you? Dr. Jonathan Rosenberg: I'm doing very well. Thanks so much for hosting today. Dr. Rana McKay: Oh, of course. It's always fun to step back from ASCO and reflect on all the practice-changing and practice-informing studies that were presented. Dr. Jonathan Rosenberg: Absolutely. Dr. Rana McKay: Maybe we can dive right in with LBA4619. This is the much-talked-about THOR study of erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer with select FGFR alterations. What are your key takeaways from this study? Dr. Jonathan Rosenberg: It is indeed a study we've been waiting for, for quite some time, to see the results in the confirmatory study after the accelerated approval of erdafitinib. This is half of the THOR trial. There were 2 cohorts of patients. One cohort were patients who previously received a checkpoint inhibitor randomized to chemotherapy or erdafitinib, and those data were reported at ASCO this year. The other cohort was randomized against a checkpoint inhibitor in patients who have not received a checkpoint inhibitor, and we'll see those data in a future meeting. The bottom line for the THOR study is that FGFR3 inhibition improved overall survival compared with chemotherapy, and the chemotherapy in this study was a taxane. The overall survival was 12.1 months for erdafitinib compared to 7.8 months for chemotherapy with a hazard ratio of 0.64. This led to the DMC to stop the study and blind the data and cross people over. There was also a PFS advantage. There really weren't a lot of new toxicity signals seen; the usual suspects in terms of mucositis, hyperphosphatemia, diarrhea, dry mouth, and onycholysis. And so, what it tells us ultimately is that in a patient who's progressed on a checkpoint inhibitor, we can feel comfortable about using erdafitinib knowing it provides a survival advantage in patients who've been previously treated for advanced urothelial cancer and have an FGFR alteration, either an FGFR2 or 3. And hopefully, we'll see more data in the future from the study, maybe not too long in the future from the other part of the study, comparing it to checkpoint inhibition. Dr. Rana McKay: That's really exciting. I think it's exciting to see the data about the positivity of erdafitinib versus chemotherapy in this context. Looking at the phase 3 data is going to be really important. Looking at the data in the IO naive context is going to be really important. I feel like this sort of reaffirms what we've been doing in clinical practice. But how do you feel that the study is practice-changing? Dr. Jonathan Rosenberg: I think it gives us reassurance that for these patients, erdafitinib is an appropriate option. There's no randomized data between erdafitinib and other choices, such as sacituzumab, which is also based on an accelerated approval, or enfortumab, which is based on randomized phase 3 trial. But it gives us level-1 evidence. I do wonder whether the comparison against the checkpoint inhibitor may turn out differently, but we'll see. Those data aren't in evidence. And I do think it was interesting that the majority of patients who were enrolled on the trial were PDL-1 low. We'll see what the comparison to a checkpoint inhibitor is like and whether those patients have similar characteristics. Dr. Rana McKay: Yeah, you're almost kind of selecting for people that were not primed to respond. Dr. Jonathan Rosenberg: Exactly. Dr. Rana McKay: Well, that's really exciting, I think. Moving on to localized bladder cancer, Dr. Pfister presented the results of the VESPER trial. That's LBA4507. I think this study was really important. This was a trial that explored dose-dense MVAC with methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine-cisplatin as a perioperative chemotherapy for muscle-invasive bladder cancer. I think there's always been some discussion around these regimens and how they pair up against one another. Can you tell us about these data? Dr. Jonathan Rosenberg: It's a very interesting study. It was designed back when it was felt that we could not give patients neoadjuvant therapy. And it was designed as either a neoadjuvant or adjuvant approach. Although, in reality, almost everybody who was enrolled in the study got neoadjuvant chemotherapy, which I think speaks to the shift in practice over the last 10 to 15 years towards neoadjuvant rather than adjuvant therapy. It's an interesting trial in that it used a duration of chemotherapy for the MVAC regimen, the dose-dense MVAC regimen that we don't usually use, which is 6 cycles. And functionally, about 40% of patients couldn't make it to 6 cycles and had to stop sooner, versus 4 cycles of q3-week gemcitabine and cisplatin. And what the data show is that the progression-free survival for the entire intent-to-treat population didn't reach significance. But if you looked at the neoadjuvant population only, there was an improvement in progression-free survival as well as overall survival. So, it's sort of a negative positive trial. Negative for the primary endpoint, but positive for key secondary endpoints. They did a very interesting analysis looking at the number of cycles that patients received regardless of arm, but looking at it by arm. And it's clear from that analysis that the more chemotherapy they got, the better they did. Although, the flaw in that analysis is that the healthier patients are, the more chemotherapy they're able to tolerate, and therefore that may translate to an improved overall survival irrespective of the amount of chemotherapy. And this was not necessarily a pre-specified analysis. I think some of the statisticians were clutching their chests during the report of this trial, having talked to several afterward. On the other hand, it does say to me that for a fit, younger patient, it is important to consider dose-dense MVAC instead of gemcitabine and cisplatin. I'll also note, reading the publication from the first part of the trial, that it appears that nobody over 70 was enrolled from everything I could tell. And so, I question the validity of the tolerability of the results for the average 75-year-old that I see in my practice. Although age is not a bright line cut-off for anybody in terms of cancer treatment. But my own experience has been that dose-dense MVAC has been harder to tolerate for a lot of patients in their 70s, whereas I think we should feel quite comfortable giving it to patients in their sixties. And if you ask me how many cycles I would give, I probably wouldn't say 6, for dose-dense MVAC, I would probably say 4. Dr. Rana McKay: Was there a predilection that there was a more aggressive disease like nodal disease or other things to prompt the 6 versus 4? Dr. Jonathan Rosenberg: I think that they stopped primarily for toxicity reasons, but it wasn't clear to me that it was a disease-based issue. And for the neoadjuvant therapy, everyone was supposed to be clinically node-negative on entry, so that probably wouldn't have explained it. Dr. Rana McKay: Very exciting. I know that the data were quite provocative, but I think it's always difficult to interpret these sorts of subgroup of subgroup analyses, and there's a lot of bias in why people may get more versus less. And I think trying to reduce these data to clinical practice is going to be really important, as you've stated. Dr. Jonathan Rosenberg: Rana, I'd also like to talk about some key advances in renal cell carcinoma that were reported at ASCO. Dr. Choueiri presented data on LBA4500, the CONTACT-03 study, which really was the first study of its kind in solid tumors because it addressed a major question in the kidney cancer field and in other fields: Is there a role for immunotherapy rechallenge after progression on immunotherapy? Specifically, the study looked at the efficacy and safety of atezolizumab plus cabozantinib versus cabozantinib alone after progression with prior immune checkpoint inhibitor therapy in metastatic RCC. I'd like you to tell me what you think of this study and the results and how they may affect our practice. Dr. Rana McKay: Absolutely. This was a critically important study looking at the role of IO post-progression on IO. It was a large phase 3 trial that enrolled patients with clear cell and non-clear cell patients. It actually allowed patients with papillary RCC, unclassified RCC, to enroll in the study, whereas most of these studies are excluding patients with non-clear cell disease. Patients had to have progressed on an immune checkpoint inhibitor given either as adjuvant first line or second line, given either as a single agent or in combination with one of the other combos, whether a VEGF or IO. And patients were randomized one-to-one to receive the combination of atezolizumab plus cabozantinib versus cabozantinib alone. And the dosing of the cabozantinib here is at 60 milligrams in the combination, which is the standard dosing of cabozantinib monotherapy. And the primary endpoints for the trial included PFS and OS. And in essence, this trial was a completely negative study. The primary endpoint, which was centrally reviewed, rPFS, was negative. The hazard ratio there was 1.03. Overall survival was also negative with a hazard ratio of 0.94. And when you look at the subgroup analyses, there really wasn't any specific subgroup that seemed to derive any benefit, potentially those that had a prior response to an immune checkpoint inhibitor, but in essence, a negative study. And I think these data are really informative because the discussion at ASCO was conducted by Dr. David Braun, and he actually had conducted a very highly scientific Twitter poll to help guide how to interpret the data and what people do. And from that, about 30% of individuals that completed the poll were actually layering on IO therapy, and continuing IO therapy after somebody progressed on therapy layering in a TKI while keeping the IO backbone going. And I think what this study proves is that we really don't have any really robust data to guide doing that at the present time. And what we may end up doing is compromising the efficacy of the oral TKI or dose-compromising the oral TKI to try to maintain an ineffective IO. And so, I think at the present time these data, while negative, were truly practice-informing. There are other studies that are looking at this strategy as well. I think one of the criticisms here is that atezolizumab really has not had a great track record in renal cell carcinoma in every single context where it was tested, either alone or in combination. It has not met its primary endpoint and it's not utilized as a treatment in RCC. So, there's some discussion that could this be the fact that this is a PDL-1 inhibitor and that it's atezolizumab. And additionally, I think the thing to point out for is that in the modern era if we look at the cabozantinib control arm, cabozantinib in the refractory setting had a PFS of 10.8 months, which is pretty impressive for a later line PFS, if you will. So, there is another study currently ongoing called the TiNivo-2 study that's looking at tivozanib plus nivolumab versus tivozanib alone in a similar patient population. That trial is enrolling only clear cell patients that had progressed on prior IO. So, I think we'll have additional data, but very, I think, informative. I think this question comes up in a lot in other tumor sites as well because of the broad use of checkpoint inhibitors across hematologic and solid tumor malignancies. Dr. Jonathan Rosenberg: I think this was the most informative negative study and the most negative trial I've seen in a while as well. But it did highlight the importance of asking these questions where people assume they know the answer already, and in fact, we often don't, and our assumptions are wrong. So, I thought that was fascinating and very well described. Staying in the kidneys arena. I'd like to talk to you also about the phase 2 KEYNOTE-B61, that's Abstract 4518. It looked at first-line lenvatinib and pembrolizumab across non-clear cell carcinomas. Tell me what you thought of the trial and what your takeaways were. Dr. Rana McKay: This is an important study. I think the treatment of non-clear cell RCC has lagged. I guess the advances have lagged behind clear cell RCC, and really robust phase 3 randomized studies in people with non-clear cell histologies are very limited. This was a single-arm phase 2, so I think we need to kind of take that for what it's worth, that enrolled patients who had non-clear cell RCC per investigator that had received no prior systemic therapy. So, this was a frontline study, and patients received pembrolizumab plus lenvatinib until disease progression or toxicity. The study enrolled a very robust 158 patients, which is pretty impressive for a modern-day non-clear cell cohort. We've seen data from nivo-cabo that had gotten presented previously by Dr. Lee. That study was a single institution, about 40 patients or so if you will. The primary endpoint of this study was objective response rate, and the bulk of the patients that were enrolled were papillary RCC. As you would imagine, around 60% of patients were papillary. It did include around 18% with chromophobe RCC. And when we break things down by IMDC risk category, about 44% of patients were favorable-risk disease. I think the percentage of patients who were favorable is higher than if we were to take an all-comer metastatic RCC patient population. But the objective response rate was pretty impressive at 49% with this combination. The CR rate was right around 5.7%. So, I think certainly a pretty solid signal of efficacy. But again, this is a single-arm phase 2 study. I think what's also really interesting, and I think we have to take subset analyses with a grain of salt if you will, but there were responses that were seen across all histologies. And the prior nivo-cabo study that I had shared with you had previously done a futility analysis for patients with chromophobe RCC, and that cohort actually closed down. And in this study, the response rate for the chromophobe patients, though it wasn't a lot of patients, 29 patients with chromophobia RCC, was around 27.6%, so I think these data are certainly informative. If you look at the waterfall plot, there were some deep responses that were certainly observed, and the bulk of patients had some degree of tumor shrinkage with very little patients that had primary PD. Dr. Jonathan Rosenberg: It's really provocative. So, are we getting to a point where we might start thinking about randomized trials in the non-clear cell population to try to establish the best standard of care? Dr. Rana McKay: Well, I think PAPMET2 is currently enrolling patients. That study is looking at the combination of cabozantinib with atezolizumab versus cabozantinib alone for frontline papillary. PAPMET1, which was led by Dr. Pal, I mean, these studies are really magnanimous because it takes all hands on deck to get these patients enrolled because they're few and far between. So, I definitely think we need to be moving in that direction. And I think we need to be moving away from lumping all non-clear cells into one bucket because I think what we're seeing is that, one, the biology of these tumors is very distinct and unique, and they don't all behave the same to any one given therapy. So, we really need to move away from just lumping all non-clear cells into one bucket and try to actually conduct studies for each specific subtype. Dr. Jonathan Rosenberg: Understood and agree. Let's switch gears for a second and talk about prostate cancer. Can you talk about the data from Abstract 5004, the TALAPRO-2 study of talazoparib and enzalutamide compared to placebo and enzalutamide as a first-line treatment with metastatic CRPC that have HR homologous recombination repair gene alterations? Dr. Rana McKay: Absolutely. So the TALAPRO-2 study is one of three studies that have looked at the combination of PARP inhibitors with an ARSI in the frontline mCRPC setting. And this trial randomized patients to talazoparib and enzalutamide versus placebo enzalutamide. And again, this was first-line mCRPC. Patients were allowed to have received prior docetaxel or prior abiraterone in the castration-sensitive setting, and the primary endpoint was overall survival. At GU ASCO this year, we saw the top-line data from TALAPRO-2 first get presented. And what was actually presented at this meeting was the subset of patients that were HRR-mutated only. They had two cohorts: an all-comer cohort that was previously presented, and then now they're presenting the subset of the patients that were HRR-mutated. And I think what we've seen across the board is that the efficacy of PARP inhibitors kind of differs by underlying HRR mutations. When we look at the entire population of HRR-deficient patients, the study was positive, talazoparib plus enzalutamide resulted in an improvement in rPFS compared to enzalutamide placebo. The hazard ratio there was 0.45. And then when we break things down by selected gene groups, they did this subset analysis in patients with only BRCA1, only BRCA2, only PALB2, only CDK12, ATM CHEK2 if you will. The data are most robust for those patients with a BRCA1/2 alteration with hazard ratios of 0.17, 0.19. Again, this is for rPFS. But then, when we look at some of these other mutations, like ATM CHEK2, hazard ratios are higher, 0.76, 0.90. So, the effect size really kind of drops off for those non-BRCA1/2 altered HRR genes. But if we look across the different subgroup analyses, the interim OS data for the HR deficient, the time to PSA, time to cytotoxic chemo, all of that favored the combination versus placebo enzalutamide for patients that were HR deficient if we just lumped everybody all together. Dr. Jonathan Rosenberg: How does this fit into the general landscape around this question with selection versus not selecting for HRR alterations? Dr. Rana McKay: The data that were presented were for the selected patients, and I think that that's not where the controversy is. I think that the selected patients are the ones that seem to derive the most benefit. It's interesting because in looking at the data from PROpel and the final FDA label based off of the PROpel data, the label is only for BRCA1 and 2 patients and not for all comer HRR. It's even a more restricted label than olaporib monotherapy. So, I think it's going to be interesting. I don't know what the right answer is. I think it's going to be interesting to see how this is going to unfold for TALAPRO-2 and even for MAGNITUDE, if you will, like, how select is the selected population going to be. But at the present time, I think the label is what it is for olaparib plus abiraterone in those BRCA1/2 frontline. My hope is that this population is shrinking because everybody should be getting escalated in the metastatic hormone-sensitive setting, and we shouldn't be having people who are naive to an ARSI in frontline mCRPC. Dr. Jonathan Rosenberg: Understood and agreed. Dr. Rana Mckay: Well, thank you so much, Jonathan, for joining me today. It's really been a pleasure kind of going through all of the compelling advances in GU cancers from ASCO. I think it was a really exciting meeting, and thanks for your time. Dr. Jonathan Rosenberg: My pleasure. It's been great to talk to you today. Dr. Rana Mckay: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Rana McKay @DrRanaMcKay Jonathan Rosenberg @DrRosenbergMSK Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures:    Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus Dr. Jonathan Rosenberg: Honoraria: UpToDate, Medscape, Peerview, Research To Practice, Clinical Care Options, Physician Education Resource, MJH Life Sciences, EMD Serono, Pfizer Consulting or Advisory Role: Lilly, Merck, Roche/Genentech, AstraZeneca/MedImmune, Bristol-Myers Squibb, Bayer, BioClin Therapeutics, QED Therapeutics, Pharmacyclics, GlaxoSmithKline, Janssen Oncology, Astellas Pharma, Boehringer Ingelheim, Pfizer/EMD Serono, Merck Therapeutics, Immunomedics, Tyra Biosciences, Infinity Pharmaceuticals, Gilead Sciences, Hengrui Pharmamedical, Alligator BioScience, Imvax Research Funding (Institution): Genentech/Roche, Seattle Genetics, Bayer, AstraZeneca, QED Therapeutics, Astellas Pharma Patents, Royalties, Other Intellectual Property (Institution): Predictor of platinum sensitivity

new york university california moving medicine staying cancer san diego patients os negative thor fda pfizer psa drs gu io astrazeneca advances pd pal bayer abstract merck prostate cancer propel novartis royalties dmc eli lilly magnitude sanofi asco vesper glaxosmithkline memorial sloan kettering cancer center bristol myers squibb pfister rcc brca1 medscape tempus pfs boehringer ingelheim gilead sciences parp bladder cancer brca2 pdl vegf crpc san diego school tki asco annual meeting jonathan rosenberg david braun emd serono hrr aveo fgfr mvac mrcc mucc choueiri seattle genetics mjh life sciences arsi dendreon roche genentech pharmacyclics janssen oncology qed therapeutics astrazeneca medimmune

ASCO23: Novel Approaches in RCC, mUC, and Prostate Cancer

ASCO eLearning Weekly Podcasts

Play Episode Listen Later May 25, 2023 24:49

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss the CLEAR study in renal cell carcinoma, a new exploratory analysis combining the TheraP and VISION trials in metastatic urothelial cancer, and compelling advances in prostate cancer and across GU oncology in advance of the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host for the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia. Today, we'll be discussing some key abstracts in GU oncology that will be featured at the 2023 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcript at asco.orgDNpod. Jeanny, it's great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4502 regarding long-term updated results on the CLEAR study. The abstract reports the final, prespecified overall survival analysis of the CLEAR trial, a four-year follow-up of lenvatinib plus pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yes, I would be happy to. So, just as a reminder, the combination of lenvatinib and pembrolizumab was initially approved by the FDA in August 2021 for first-line treatment of adult patients with advanced renal cell carcinoma. So, this was based on significant benefits that were seen in progression-free survival, which was a primary endpoint, but also showed improvement in the overall response rates compared with sunitinib in first-line advanced renal cell carcinoma. So this abstract reports on longer-term follow-up now at a median of 49.8 months, and PFS favored the combination lenvatinib and pembrolizumab compared to sunitinib across all MSKCC risk groups, and PFS benefit versus lenvatinib and pembro compared to sunitinib was maintained with a hazard ratio of 0.47. And even overall survival was also maintained with the combination with a hazard ratio of 0.79, and the overall survival favored the combination across all risk groups. If we look at the CR rate, it was 18.3% for the combination compared to 4.8% with sunitinib, unless patients in the combination arm received subsequent anticancer therapies, and that's intuitive. And the PFS2 was also longer with the combination at 43 months compared to 26 months. Now, it is important to note that grade III or more treatment-related adverse events did occur in about 74% of the patients in the combination of lenvatinib and pembro, compared to 60.3% in patients with sunitinib. Dr. Neeraj Agarwal: Jeanny, this is good news. So the main message from the abstract is that sustained results from this combination of lenvatinib plus pembrolizumab are being seen even after a longer follow-up of more than four years. Dr. Jeanny Aragon-Ching: Yes, I agree. So now, moving on, Neeraj, to a different setting in the RCC space, let's look at Abstract 4519, which is titled “Efficacy of First-line Immunotherapy-based Regimens in Patients with Sarcomatoid and/or Rhabdoid Metastatic Non-Clear Cell RCC: Results from the IMDC,” which will be discussed by Dr. Chris Labaki. So, Neeraj, based on this abstract, can you tell us a little bit more about the impact of these adverse pathologic risk features in non-clear cell RCC? Dr. Neeraj Agarwal: Of course. So, using real-world patient data, the IMDC investigators compared the outcomes of patients with metastatic non-clear cell RCC who were treated with immunotherapy-based combination regimens versus those who were treated with VEGF-TKIs alone. They also assessed the impact of sarcomatoid and rhabdoid features on response to IO-based combinations versus VEGF-TKIs. Of 103 patients with metastatic non-clear cell RCC who had rhabdoid or sarcomatoid features, 32% of patients were treated with immunotherapy-based combinations. After adjusting for confounding factors, the authors show that those treated with a combination of two immune checkpoint inhibitors or an immune checkpoint inhibitor with a VEGF-TKI combination had significantly improved overall survival, which was not reached in the immunotherapy combination group versus seven months within the VEGF-TKI group. Time to treatment failure and objective responses were also prolonged, significantly higher, and better in the immunotherapy groups compared with patients who were treated with VEGF-TKIs alone. Interestingly, if you look at those 430 patients with metastatic non-clear cell RCC who did not have sarcomatoid or rhabdoid features, they didn't seem to benefit with immunotherapy-based combinations. Dr. Jeanny Aragon-Ching: This is an exciting update, Neeraj. What are the key takeaways from this abstract? Dr. Neeraj Agarwal: So the main takeaway is if you see a patient with advanced non-clear cell RCC who has sarcomatoid and rhabdoid features, there appears to be a rather substantial and selective benefit with IO-based combinations. And in this context, I would like to highlight the ongoing SWOG 2200 trial also known as PAPMET2 trial, which is comparing the combination of cabozantinib plus atezolizumab. So immuno-therapy-based combinations versus cabozantinib alone in advanced papillary renal cell carcinoma setting. So this trial is being led by Dr. Benjamin Maughan and Dr. Monty Pal. And I like to encourage our listeners to consider referring their patients for involvement in this federally funded trial so that we can validate the data from this retrospective study in a prospective way. So, Jeanny, let's now move on to another important disease type which is urothelial carcinoma. There is a very recent accelerated FDA approval of the drug combination of enfortumab vedotin and pembrolizumab for cisplatin-ineligible metastatic urothelial carcinoma patients. This is Abstract 4505, which is being presented by Dr. Shilpa Gupta and colleagues. Can you please tell us more about this update? Dr. Jeanny Aragon-Ching: Yeah, absolutely. So, as you mentioned, Neeraj, the FDA just granted accelerated approval in April 2023 for this combination of enfortumab vedotin or EV, which is and ADC, antibody drug conjugate against nectin-4 and the PD-1 inhibitor pembroluzimab. So it's a combination for patients with locally advanced or metastatic urothelial carcinoma who are considered cisplatin ineligible. So this is nearly a four-year follow-up. So as a reminder, this was a phase 1b/2 trial that included 45 patients and it had a primary endpoint of safety and tolerability although the key secondary endpoints included confirmed overall responses, duration of response, progression-free survival, and the resist criteria was investigated via investigator and BICRs which is in a blinded independent central review. Even overall survival was a key secondary endpoint. So, the bottom line was the confirmed overall response by BICR was 73.3%, the disease control rate was about 84%, and the CR rate was 15.6% with a PFS of close to 13 months, and a 12-month overall survival rate of 83%. However, it is important to cite that there were treatment-related adverse events including skin reactions in 66%, neuropathy occurred in 62%, and ocular disorders in 40%. And there was a little bit of pneumonitis in close to 9%, colitis, and hypothyroidism, so there are side effects to watch out for. Dr. Neeraj Agarwal: So, Jeanny this is great. What is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: So I think the most important thing is we now have a new combination of EV and pembro which shows very promising responses and survival in part which led to the FDA accelerated approval in the cisplatin-ineligible population of patients. However, we must note that the phase 3 trial of EV302 will ultimately establish which approach is really beneficial for all of our cisplatin-ineligible patients, either a carboplatin-based chemotherapy regimen or a non-platinum-based regimen such as EV and pembro. Dr. Neeraj Agarwal: Thanks Jeanny, would you like to discuss any other study in the bladder cancer space? Dr. Jeanny Aragon-Ching: Absolutely. I think Abstract 4508 from Dr. Seth Lerner and colleagues will be very relevant to our colleagues. This abstract is SWOG S1011, which is a phase 3 surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at the time of radical cystectomy for muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Yes. So this trial, as you said, is an important trial which randomized in a one-on-one fashion 618 patients with muscle-invasive bladder cancer undergoing radical cystectomy, and these patients were randomized to either standard lymph node dissection or an extended lymph node dissection. And standard lymph node dissection included, as we know, external and internal iliac and operative lymph node. The extended lymph node dissection included lymph nodes up to aortic bifurcation which included common iliac, presciatic, and presacral lymph nodes. At a median follow-up of approximately 6 years, there was no disease-free survival or overall survival benefit in patients undergoing an extended lymph node dissection compared to standard lymph node dissection. And extended lymph node dissection was also associated with greater morbidity and preoperative mortality. Dr. Jeanny Aragon-Ching: Very interesting data, Neeraj. So these results, I think, will be very useful for a lot of our surgical colleagues in both academia and the community who may still be inclined to perform extended lymphadenectomy during cystectomy. This study shows that it's actually not necessary. Dr. Neeraj Agarwal: Absolutely. So now let's move on to another disease type, which is very important - prostate cancer. There are several practice-informing abstracts that are worthwhile discussing. The first of these involves Abstract 5002, which looks at the impact of the PSA nadir as a prognostic factor after radiation therapy for localized prostate cancer, which will be presented by Dr. Praful Ravi and colleagues. Jeannie, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, definitely. So this abstract, as you mentioned, Neeraj, is a prognostic impact of PSA nadir of more than or equal to 0.1 nanogram per ml within six months after completion of radiotherapy for localized prostate cancer - an individual patient data analysis of randomized trials from the ICECaP Collaborative. Basically, it refers to an attempt to evaluate early surrogate measures to predict for long term outcomes such as prostate cancer-specific survival, metastases-free survival, and overall survival. So they looked at a big registry from the ICECaP collaboration that included 10,415 patients across 16 randomized controlled trials. And those men underwent treatment for intermediate risk and high risk prostate cancer treated with either radiation therapy alone in about a quarter of patients, or they got RT with short-term ADT in about 58% of patients, and 17% of them got RT with long-term ADT. So, after a median follow-up of ten years, what they found was, if you had a PSA nadir that is over or equal to 0.1 nanogram per ml within six months after completion of radiation therapy, it was associated with worse prostate cancer-specific survival, metastases-free survival, and overall survival. For instance, the five-year metastases-free survival for those who achieved a PSA nadir of less than 0.1 was 91% compared to those who did not, which was 79%. Therefore, they concluded that if you achieve a bad PSA of 0.1 or above within six months after you completed radiation, you had worse outcomes. Dr. Neeraj Agarwal: Jeanny, what is the key takeaway message from this study? Dr. Jeanny Aragon-Ching: The key takeaway from this ICECaP analysis is that this information would be very important to augment a signal-seeking endpoint, especially for clinical trial development, so that we can develop further strategies to de-escalate for those who don't need systemic intensification or therapy intensification versus escalation for those who really do. Dr. Neeraj Agarwal: So, my radiation oncology colleagues need to watch out for those patients who do not achieve a PSA of less than 0.1 nanogram per ml within the first six months of finishing radiation therapy. Very interesting data. Dr. Jeanny Aragon-Ching: Yes, absolutely. So. Neeraj another important abstract for our fellow clinicians, switching gears a little bit now, is Abstract 5011, which is titled “Do Bone Scans Overstage Disease Compared to PSMA PET?” This was an international, multicenter retrospective study with blinded, independent readers. Can you tell us more about this abstract? Dr. Neeraj Agarwal: Yes, a relatively small retrospective study, but still pertinent to our practice. So I'll summarize it. This study by Dr. Wolfgang Fendler and colleagues evaluated the ability of bone scans to detect osseous metastasis using PSMA PET scan as a reference standard. So in this multicenter retrospective study, 167 patients were included, of which 77 patients were at the initial staging of prostate cancer, 60 had biochemical recurrence after definitive therapy, and 30 patients had CRPC or castor-resistant disease. These patients had been imaged with a bone scan and a PSMA PET scan within 100 days. And in all patients, the positive predictive value, negative predictive value and specificity for bone scan were evaluated at different time points. They had bone scan and PSMA PET scan and both were compared. And what they found was interesting. All these three values - positive predictive value, negative predictive value, and specificity for bone scan were 0.73, 0.82 and 0.82 in all patients, and in initial staging, it was even lower at 0.43 and 0.94 and 0.80. So, without getting into too much detail regarding these numbers, I want to highlight the most important part of the study, that at the initial staging, 57% patients who had a positive bone scan had false positive bone scans. The interreader agreement for bone disease was actually moderate for bone scans and quite substantial for the PSMA PET scan. Dr. Jeanny Aragon-Ching: So, Neeraj, what do you think is the key takeaway message here for our audience? Dr. Neeraj Agarwal: The key takeaway message is that positive predictive value of bone scan was low in prostate cancer patients at initial staging, with the majority of positive bone scans being false positive. This suggests that a large proportion of patients which we consider to have low-volume metastatic disease by bone scan actually have localized disease. So in the newly diagnosed patients with prostate cancer, patients should ideally have a PSMA PET scan to rule out metastatic disease. So, let's move on to another abstract I would like to discuss, which has important implications in treatment, especially now that lutetium 177 is approved, but frankly not available widely. Dr. Jeanny Aragon-Ching: Yeah, that's actually very timely. So the abstract you're referring to is 5045, which is being presented by Dr. Yu Yang Sun and colleagues entitled “Effects of Lutetium PSMA 617 on Overall Survival in TheraP Versus VISION Randomized Trials: An Exploratory Analysis.” So, Neeraj, can you tell us more about the relevance of this exploratory analysis? Dr. Neeraj Agarwal: Definitely. In this abstract, Dr. Yang Sun and colleagues assess the effect of lutetium PSMA on overall survival in two different trials, TheraP and VISION trials. So, just for our listeners' recollection, the phase 2 TheraP trial compared lutetium PSMA and cabazitaxel in patients with mCRPC who had progression on docetaxel and had significant PSMA avidity on gallium PSMA pet scan, which was defined as a minimum uptake of SUV max of 20 at least one site of disease and SUV max of more than 10 at all sites of measurable disease. In this trial, 20 of 101 patients in the cabazitaxel arm crossed over to lutetium PSMA, and 32 of 99 patients in the lutetium PSMA arm crossed over to cabazitaxel. In the VISION trial, patients with mCRPC who previously progressed on at least one ARPI and one taxane-based therapy and had a positive gallium PSMA scan, and here, positivity was not stringently pre-specified as it was done in the context of TheraP trial. So, positive gallium pet scans were randomly assigned in two to one fashion to receive either lutetium PSMA plus best supportive care or standard of care versus standard of care. And I'd like to highlight that the standard of care comprised ARPIs and bone protecting agents and these patients were not allowed to have cytotoxic chemotherapy such as cabazitaxel in the standard of care arm. Now, overall survival was similar in the lutetium PSMA group regardless of whether they got lutetium PSMA in the VISION trial or TheraP trial. There was no difference in overall survival with lutetium in the lutetium arms of VISION and TheraP trial with a hazard ratio of 0.92. And there was no difference in the overall survival between the lutetium PSMA and the cabazitaxel group in the TheraP trial if you use counterfactual analysis, assuming crossover had not occurred. So, quite interesting in my view. Dr. Jeanny Aragon-Ching: Yeah, thanks Neeraj for that wonderful synopsis and discussion. So, what is the key take home message then? Dr. Neeraj Agarwal: The main message in this new exploratory analysis, which combined both the TheraP and VISION trials, is that lutetium PSMA and cabazitaxel seem to be associated with similar overall survival benefit in these highly selected patients with PSMA positivity. Additionally, the difference in the observed effect of lutetium PSMA and overall survival in the TheraP and VISION trials may be actually better explained by the use of different treatments in the respective control arms of these trials. And these results, in my view, are quite pertinent for those patients and providers who do not have access to lutetium-177 therapy. Let's go to another abstract that is currently relevant to our practice, given many patients with advanced prostate cancer who have concurrent diabetes; I'm talking about Abstract 5066. Jeanny, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Certainly, Neeraj. So this abstract will be presented by Dr. Amy Shaver and colleagues. So it's also very relevant, since many men who are diagnosed with prostate cancer frequently also have a concomitant diagnosis of type 2 diabetes mellitus. So, this was a SEER-Medicare population database analysis that looked at men who were treated with either abiraterone or enzalutamide and also had concomitant diagnosis of type 2 diabetes mellitus (DM). And they were identified using ICD-9 and ICD-10 codes and they were all tied in to acute care utilization. So they looked at CMS research data codes and ER hospitalization visits six months after treatment initiation was recorded. So all in all, they took a sample of 11,163 men, of whom close to 62% were treated with abiraterone and about 38% were treated with enzalutamide. So, of these, about 27% of them had type 2 DM, of whom 59% received abiraterone and about 41% had enzalutamide. So, the bottom line is, compared to those without diabetes mellitus, those who had type 2 diabetes had worse acute care utilization, which was 43% higher than those who got abiraterone compared to enzalutamide, and also had higher overall mortality. Therefore, the bottom line is, having type 2 diabetes mellitus, unfortunately, portends worse outcomes in men with prostate cancer, so careful attention needs to be paid to those who are starting out already with such comorbidities. So Neeraj, any final thoughts you have regarding this abstract and overall before we wrap up on the podcast today? Dr. Neeraj Agarwal: Absolutely. So it looks like, based on this very important pertinent Abstract 5066, which talks about the impact of diabetes on our patients, I think we need to be very watchful regarding the impact of diabetes on our patients who are being treated with abiraterone or enzalutamide, especially drugs which are known to make the metabolic syndrome and diabetes worse. I think close monitoring and close attention to control of diabetes is very important. So with that, I would urge the listeners to come and join us at the Annual Meeting, not only to celebrate these successes but also to help disseminate this cutting-edge data to practitioners and maximize the benefit to our patients across the globe. And thank you to our listeners for joining us today. You will find links to the abstracts we discussed today on the transcript of this episode. Finally, if you value the insights that you hear on our ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.

university time vision speaker er dm patients clear effects consulting fda pfizer psa ev gu io astrazeneca suv rt pd bayer cms abstract merck efficacy prostate cancer annual meetings janssen novartis agarwal immunotherapy sanofi asco genentech amgen disclosures icd bristol myers squibb adt takeda adc rcc pfs gilead sciences bladder cancer nektar crpc eisai asco annual meeting novel approaches psma icecap emd serono jeanny foundation medicine aveo crispr therapeutics mskcc medimmune arpi swog seattle genetics therap psma pet dendreon pharmacyclics arvinas janssen oncology transcript dr neeraj agarwal mei pharma

Cancer Topics – Research to Practice: Prostate Cancer (Part 1)

Play Episode Listen Later May 10, 2023 27:13

In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. The first scenario involves a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:12), review research evidence regarding systemic and radiation therapy for high-risk localized disease (5:45), and reflect on the importance of genetic testing and (10:57) and considerations for treatment approaches at progression to metastatic disease (16:13). Speaker Disclosures Dr. Kriti Mittal: Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group Research Funding - Pfizer Dr. Jorge Garcia: Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology; Genentech/Roche; Lilly Other Relationship - FDA Resources ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today we'll explore how we interpret and integrate recently reported clinical research into practice, focusing on two clinical scenarios: localized prostate cancer progressing to hormone-sensitive metastatic disease; and a case of de novo metastatic hormone-sensitive prostate cancer progressing to castration-resistant disease. My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist chair and the current chair of the Solid Tumor Oncology Division at University Hospital's Seidman Cancer Center. Let me begin by presenting the first patient scenario. Case 1: A 72-year-old male was referred to urology for evaluation of hematuria. A rectal exam revealed an enlarged prostate without any nodules. A CT urogram was performed that revealed an enlarged prostate with bladder trabeculations. A cystoscopy revealed no stones or tumors in the bladder, but the prostatic urethra appeared to be abnormal looking. Transurethral resection of the prostate was performed. The pathology revealed Gleason score 4+5=9 prostate cancer, involving 90% of the submitted tissue. PSA was performed one week later and was elevated at 50. Patient declined the option of radical prostatectomy and was referred to radiation and medical oncology. So I guess the question at this point is, Dr. Garcia, in 2023, how do you stage patients with high-risk localized prostate cancer and how would you approach this case? Dr. Jorge Garcia: That's a great question and a great case, by the way, sort of what you and I in our practice will call ‘bread and butter'. Patients like this type of case that you just presented come from different places to our practice. So either they come through urology or oftentimes they may come through radiation oncology. And certainly, it depends where you practice in the United States, at ‘X', US, they may come through medical oncology. So I think that the first question that I have is in whatever role I'm playing in this case, where the patient has seen a urologist or a rad onc or me first, I think it's important for us in medical oncology, at least in the prostate cancer space, to talk about how do we think of their case and put those comments into context for the patient. It's very simple for you to tell a patient you can probably have surgery, radiation therapy, but at the end of the day, how do you counsel that patient as to the implications of the features of his disease is going to be really important. I use very simple examples that I relate to my patients, but really this patient is a patient that has very high-risk prostate cancer based upon the NCCN guidelines and how we actually stratify patients into what we call low-risk, intermediate-, and high-risk, and between those very low and very high risk. So his PSA is high, very high, I would argue. His Gleason score, now, what we call group grading is high. He has high-volume disease. So the first question that I would have is, what are the choices for treatment for a patient like this? But even before you and I may talk about treatment options, we really want to understand the volume of their disease and whether or not they have localized prostate cancer with high-risk features or whether or not they have locally advanced or hopefully not metastatic disease. So back in the days prior to the FDA approval for PSMA PET imaging, we probably will have a Technetium-99 whole-body bone scan, and/or we probably will actually use CT scanning. Most people in the past, we used to do just a CT of the abdomen and pelvic region. As you know, with the movement of oral agents in the advanced setting, I think most of us will do a chest CT, abdomen and pelvic region, and certainly we also probably will have a Technetium-99 bone scan. Now, with the utility and the use of PET imaging, I think most people like him will probably undergo PET PSMA, where you use F-18 PSMA or Gallium-68 PSMA. I think the importance depends on how you look at the approval of these two technologies. I think that PET PSMA imaging is here to stay. It's probably what most of us will use. And based upon that, we will define yet the truest stage of this patient. So right now, what we know is he has high-risk features. Hopefully, their disease is localized. We'll probably put the patient through an imaging technology. If you don't have access to a PET, then obviously CT and a bone scan will do. But if you do, the PET will actually help us define if the patient has disease outside of the prostate region, in the pelvic area, or even if they have distant metastases. Dr. Kriti Mittal: I would agree with that approach, Dr. Garcia. I think in the United States, we've been late adopters of PSMA scans. I think this patient with high-risk localized disease, if insurance allows at our institution, would get a PSMA for staging. There are still some patients where insurance companies, despite peer-to-peer evaluations, are not approving PSMAs. And in those situations, the patient would benefit from conventional CTs and a bone scan. So let's say this patient had a PSMA and was found not to have any regional or distant metastases. He decided against surgery, and he is seeing you as his medical oncologist together with radiation. What would your recommendations be? Dr. Jorge Garcia: I think the bigger question is, do we have any data to suggest or to demonstrate that if in the absence of metastatic disease with conventional imaging or with emerging technologies such as PSMA PET, there is no evidence of distant disease, which I think you probably agree with me, that would be sort of unlikely with a patient with these features not to have some form of PSMA uptake somewhere in their body. But let's assume that indeed then the PSMA PET was negative, so we're really talking about high-risk localized prostate cancer. So I don't think we can tell a patient that radical prostatectomy would not be a standard of care. We never had a randomized trial comparing surgery against radiation therapy. This patient has already made that decision and surgery is not an option for him. If he, indeed, had elected radiotherapy, the three bigger questions that I ask myself are where are you going to aim the beam of that radiation therapy? What technology, dose, and fractionation are you going to use? And lastly, what sort of systemic therapy do you need, if any, for that matter? Where we do have some data maybe less controversial today in 2023 compared to the past? But I think the question is, do we do radiation to the prostate only or do we expand the field of that radiation to include the pelvic nodes? Secondly, do we use IMRT? Do you use proton beam or not? Again, that's a big question that I think that opens up significant discussions. But more important, in my opinion, is the term of hypofractionation. I think the field of radiation oncology has shifted away from the old standard, five, seven weeks of radiation therapy to more hypofractionation, which in simple terms means a higher dose over a short period of time. And there was a concern in the past that when you give more radiation on a short period of time, toxicities or side effects would increase. And I think that there is plenty of data right now, very elegant data, demonstrated that hypofractionation is not worse with regards to side effects. I think most of us will be doing or supporting hypofractionation. And perhaps even to stretch that, the question now is of SBRT. Can we offer SBRT to a selected group of patients with high-risk prostate cancer? And again, those are discussions that we will naturally, I assume, in your practice, in your group, you probably also have along with radiation oncology. Now, the bigger question, which in my mind is really not debatable today in the United States, is the need for systemic therapy. And I think we all will go back to the old data from the European EORTC data looking at the duration of androgen deprivation therapy. And I think most of us would suggest that at the very least, 24 months of androgen deprivation therapy is the standard of care for men with high-risk prostate cancer who elect to have local definitive radiation therapy as their modality of treatment. I think that whether or not it's 24 or 36, I think that the Canadian data looking at 18 months didn't hit the mark. But I think the radiation oncology community in the prostate cancer space probably has agreed that 24 months clinically is the right sort of the sweetest spot. What I think is a bit different right now is whether or not these patients need treatment intensification. And we have now very elegant data from the British group and also from the French group, suggesting, in fact, that patients with very high-risk prostate cancer who don't have evidence of objective metastasis may, in fact, benefit from ADT plus one of the novel hormonal agents, in this case, the use of an adrenal biosynthesis inhibitor such as abiraterone acetate. So I think in my practice, what I would counsel this patient is to probably embark on radiotherapy as local definitive therapy and also to consider 24 months of androgen deprivation therapy. But I would, based upon his Gleason score of group grading, his high-volume disease in the prostate gland, and his PSA, to probably consider the use of the addition of abiraterone in that context. Dr. Kriti Mittal: That is in fact how this patient was offered treatment. The patient decided to proceed with radiation therapy with two years of androgen deprivation. And based on data from the multi-arm STAMPEDE platform, the patient met two of the following three high-risk features Gleason score >8, PSA >40, and clinical >T3 disease. He was offered two years of abiraterone therapy. Unfortunately, the patient chose to decline upfront intensification of therapy. In addition, given the diagnosis of high-risk localized prostate cancer, the patient was also referred to genetic counseling based on the current Philadelphia Consensus Conference guidelines. Germline testing should be considered in patients with high-risk localized node-positive or metastatic prostate cancer, regardless of their family history. In addition, patients with intermediate-risk prostate cancer who have cribriform histology should also consider germline genetic testing. Access to genetic counseling remains a challenge at several sites across the US, including ours. There is a growing need to educate urologists and medical oncologists to make them feel comfortable administering pretest counseling themselves and potentially ordering the test while waiting for the results and then referring patients who are found to have abnormalities for a formal genetics evaluation. In fact, the Philadelphia Consensus Conference Guideline offers a very elegant framework to help implement this workflow paradigm in clinical practice. And at our site, one of our fellows is actually using this as a research project so that patients don't have to wait months to be seen by genetics. This will have implications, as we will see later in this podcast, not only for this individual patient as we talk about the role of PARP inhibitors but also has implications for cascade testing and preventative cancer screening in the next of kin. Dr. Jorge Garcia: Dr. Mittal, I think that we cannot stress enough the importance of genetic testing for these patients. Oftentimes I think one of the challenges that our patients are facing is how they come into the system. If you come through urology, especially in the community side, what I have heard is that there are challenges trying to get to that genetic counsel. Not so much because you cannot do the test, but rather the interpretation of the testing and the downstream effect as you're describing the consequences of having a positive test and how you're going to counsel that patient. If you disregard the potential of you having an active agent based upon your genomic alteration, is the downstream of how your family may be impacted by a finding such as the DNA repair deficiency or something of that nature. So for us at major academic institutions because the flow how those patients come through us, and certainly the bigger utilization of multi-disciplinary clinics where we actually have more proximity with radiation oncology urology, and we actually maybe finesse those cases through the three teams more often than not, at least discuss them, then I think that's less likely to occur. But I think the bigger question is the timing of when we do testing and how we do it. So there are two ways -- and I'd love to hear how you do it at your institution -- because there are two ways that I can think one can do that. The low-hanging fruit is you have tissue material from the biopsy specimen. So what you do, you actually use any of the commercial platforms to do genomic or next-generation sequencing or you can do in-house sequencing if your facility has an in-house lab that can do testing. And that only gets you to what we call ‘somatic testing', which is really epigenetic changes over time that are only found in abnormal cells. It may not tell you the entire story of that patient because you may be missing the potential of identifying a germline finding. So when you do that, did you do germline testing at the same time that you do somatic testing or did you start with one and then you send to genetic counseling and then they define who gets germline testing? Dr. Kriti Mittal: So at our site, we start with germline genetic testing. We use either blood testing or a cheek swab assay and we send the full 84-gene multigene panel. Dr. Jorge Garcia: Yeah, and I think for our audience, Dr. Mittal, that's great. I don't think you and I will be too draconian deciding which platform one uses. It's just that we want to make sure that at least you test those patients. And I think the importance of this is if you look at the New England Journal paper from many years ago, from the Pritchard data looking at the incidence of DNA repair deficiency in men with prostate cancer in North America, that was about what, around 10% or so, take it or leave it. So if you were to look only for germline testing, you only will, in theory, capture around 10% of patients. But if you add somatic changes that are also impacting the DNA pathway, then you may add around 23%, 25% of patients. So we really are talking that if we only do one type of testing, we may be missing a significant proportion of patients who still may be candidates, maybe not for family counseling if you had a somatic change, rather than germline testing, the positivity, but if you do have somatic, then you can add into that equation the potential for that patient to embark on PARP inhibitors down the road as you stated earlier. It may not change how we think of the patient today, or the treatment for that matter. But you may allow to counsel that patient differently and may allow to sequence your treatments in a different way based upon the findings that you have. So I could not stress the importance of the NCCN guidelines and the importance of doing genetic testing for pretty much the vast majority of our patients with prostate cancer. Dr. Kriti Mittal: Going back to our patient, three years after completion of his therapy, the patient was noted to have a rising PSA. On surveillance testing, his PSA rose from 0.05 a few months prior to 12.2 at the time of his medical oncology appointment. He was also noted to have worsening low back pain. A PSMA scan was performed that was noteworthy for innumerable intensely PSMA avid osseous lesions throughout his axial and appendicular skeleton. The largest lesion involved the right acetabulum and the right ischium. Multiple additional sizable lesions were seen throughout the pelvis and spine without any evidence of pathologic fractures. So the question is, what do we do next? Dr. Jorge Garcia: The first question that I would have is, the patient completed ADT, right? So the patient did not have treatment intensification, but at the very least he got at least systemic therapy based upon the EORTC data. And therefore, one would predict that his outcome will have been improved compared to those patients who receive either no ADT or less time on ADT. But what I'm interested in understanding is his nadir PSA matters to me while he was on radiation and ADT. I would like to know if his nadir PSA was undetectable, that's one thing. If he was unable to achieve an undetectable PSA nadir, that would be a different thought process for me. And secondly, before I can comment, I would like to know if you have access to his testosterone level. Because notably, what happens to patients like this maybe is that you will drive down testosterone while you get ADT, PSAs become undetectable. Any of us could assume that the undetectability is the result of the radiation therapy. But the true benefit of the combination of radiation and ADT in that context really comes to be seen when the patient has got off the ADT, has recovered testosterone, and only when your testosterone has normalized or is not castrated, then we'll know what happens with your serologic changes. If you rise your PSA while you recover testosterone, that is one makeup of patient. But if you rise your PSA while you have a testosterone at the castrated level, that would be a different makeup of a patient. So do we have a sense as to when the patient recovered testosterone and whether or not if his PSA rose after recovery? Dr. Kriti Mittal: At the time his PSA rose to 12, his testosterone was 275. Dr. Jorge Garcia: Okay, perfect. You and I would call this patient castration-naive or castration-sensitive. I know that it's semantics. A lot of people struggle with the castration-naive and castration-sensitive state. What that means really to me, castration-naive is not necessarily that you have not seen ADT before. It's just that your cancer progression is dependent on the primary fuel that is feeding prostate cancer, in this case, testosterone or dihydrotestosterone, which is the active metabolite of testosterone. So in this case, recognizing the patient had a testosterone recovery and his biochemical recurrence, which is the rising of his PSA occur when you have recovery of testosterone, makes this patient castration-sensitive. Now the PET scan demonstrates now progression of his disease. So clearly he has a serologic progression, he has radiographic progression. I assume that the patient may have no symptoms, right, from his disease? Dr. Kriti Mittal: This patient had some low back pain at the time of this visit. So I think we can conclude he has clinical progression as well. Dr. Jorge Garcia: Okay, so he had the triple progression, serologic, clinical, and radiographic progression. The first order of business for me would be to understand the volume of his disease and whether we use the US CHAARTED definition of high volume or low volume, or whether we use the French definition for high volume from Latitude, or whether we use STAMPEDE variation for definition, it does appear to me that this patient does have high-volume disease. Why? If you follow the French, it's a Gleason score of >8, more than three bone metastases, and the presence of visceral disease, and you need to have two out of the three. If you follow CHAARTED definition, we did not use Gleason scoring, the US definition. We only use either the presence of visceral metastases or the presence of more than four bone lesions, two of which had to be outside the appendicular skeleton. So if we were to follow either/or, this patient would be high-volume in nature. So the standard of care for someone with metastatic disease, regardless of volume, is treatment intensification, is you suppress testosterone with androgen deprivation therapy. And in this case, I'd love to hear how you do it in Massachusetts, but here, for the most part, I would actually use a GnRH agonist-based approach, any of the agents that we have. Having said that, I think there is a role to do GnRH antagonist-based therapy. In this case, degarelix, or the oral GnRH antagonist, relugolix, is easier to get patients on a three-month injection or six-month injection with GnRH agonist than what it is on a monthly basis. But I think it's also fair for our audience to realize that there is data suggesting that perhaps degarelix can render testosterone at a lower level, meaning that you can castrate even further or have very low levels of testosterone contrary to GnRH agonist-based approaches. And also for patients maybe like this patient that you're describing, you can minimize the flare that possibly you could get with a GnRH agonist by transiently raising the DHT before the hypothalamic-pituitary axis would shut it down. So either/or would be fine with me. Relugolix, as you know, the attraction of relugolix for us right now, based upon the HERO data, is that you may have possibly less cardiovascular side effects. My rationale not to use a lot of relugolix when I need treatment intensification is quite simple. I'm not aware, I don't know if you can mitigate or minimize that potential cardiovascular benefit by adding abiraterone or adding one of the ARIs, because ARIs and abiraterone by themselves also have cardiovascular side effects. But either/or would be fine with me. The goal of the game is to suppress your male hormone. But very important is that regardless of volume, high or low, every patient with metastatic disease requires treatment intensification. You can do an adrenal biosynthesis inhibitor such as abiraterone acetate. You can pick an androgen receptor inhibitor such as apalutamide or enzalutamide if that's the case. The subtleties in how people feel comfortable using these agents, I think, none of us – as you know, Dr. Mittal - can comment that one oral agent is better than the other one. Independently, each of these three oral agents have randomized level 1, phase III data demonstrating survival improvement when you do treatment intensification with each respective agent. But we don't have, obviously, head-to-head data looking at this. What I think is different right now, as you know, is the data with the ARASENS data, which was a randomized phase III trial, an international effort looking at triple therapy, and that is male hormone suppression plus docetaxel-based chemotherapy against testosterone suppression plus docetaxel-based chemotherapy plus the novel androgen receptor inhibitor known as darolutamide. This trial demonstrated an outcome survival improvement when you do triple therapy for those high-volume patients. And therefore, what I can tell you in my personal opinion and when I define a patient of mine who is in need of chemotherapy, then the standard of care in my practice will be triple therapy. So if I know you are a candidate for chemotherapy, however, I make that decision that I want you to get on docetaxel upfront. If you have high-volume features, then the standard of care would not be ADT and chemo alone, it would be ADT, chemo, and darolutamide. What I don't know, and what we don't know, as you know, is whether or not triple therapy for a high-volume patient is better, the same, equivalent, or less than giving someone ADT plus a novel hormonal agent. That is the data that we don't have. There are some meta-analyses looking at the data, but I can tell you that at the very least, if you prefer chemo, it should be triple therapy. If you prefer an oral agent, it certainly should be either apalutamide, abiraterone acetate, and/or enzalutamide. But either/or, patients do need treatment intensification, and what is perplexing to me, and I know for you as well, is that a significant proportion of our patients in North America are still not getting treatment intensification, which is really sub-optimal and sub-standard for our practice. Dr. Kriti Mittal: Thank you, Dr. Garcia, for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. In an upcoming podcast, we will continue that discussion exploring management of de novo metastatic prostate cancer. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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ARASENS, TRITON3, and Other Key Advances at GU23

Play Episode Listen Later Feb 13, 2023 26:09

Guest host Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss several crucial studies that will be presented at the 2023 ASCO Genitourinary Cancers Symposium, including ARASENS, TRITON3, and others in prostate cancer, as well as novel therapies in mRCC and urothelial carcinoma. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome Dr. Jeanny Aragon-Ching, a medical oncologist and the clinical program director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia. Today we will be discussing key abstracts in genitourinary oncology that will be featured at the 2023 ASCO Genitourinary Cancers Symposium. Our full disclosures are available in the show notes, and disclosures for all guests on the podcast can be found on our transcripts at asco.org/podcasts. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: So Jeanny, let's begin with Abstract 15 on the update on the ARASENS trial, which Dr. Maha Hussain will present [at the meeting]. In March ‘22, as we know, almost a year ago, the results of the ARASENS trials were published in the New England Journal of Medicine. Darolutamide, which is an AR signaling inhibitor plus androgen deprivation therapy plus docetaxel chemotherapy, significantly reduced the risk of death by 32.5% versus placebo plus ADT plus docetaxel. The effect of triplet therapy, including darolutamide on overall survival, was consistent across prespecified subgroups. However, survival outcomes by disease volume were not reported at the time. Can you please tell us about Abstract 15? Dr. Jeanny Aragon-Ching: Yeah, thank you so much, Neeraj, I would be happy to. So, this new data is actually very crucial for all clinicians. The title of this abstract is “Efficacy and Safety of Darolutamide in Combination with ADT and Docetaxel by Disease Volume and Disease Risk in the Phase 3 ARASENS Study.” So, as a quick reminder, in this trial, patients were randomized 1:1 to the standard dose of darolutamide 600 milligrams twice daily or placebo with ADT and docetaxel in the metastatic hormone-sensitive prostate cancer setting. Now remember, too, high volume disease was defined per the charted criteria, which is visceral metastases and/or four or more bone lesions, of which at least one or more has to be beyond the vertebral column or pelvis. 8And high-risk disease was actually defined per the LATITUDE criteria, which is any two or more of the following three factors: Gleason scores eight or more, bone lesions that are three or more, and the presence of measurable visceral metastases. Of all the 1,305 patients, 77% of them were actually classified as having high-volume disease, and 70% of them had high-risk disease. So, in both of these high-volume and low-volume disease patients, the triplet therapy darolutamide, ADT, and docetaxel actually improved overall survival and hazard ratio was 0.69 and 0.68, respectively. Compared to the placebo and ADT, and docetaxel arm. So overall survival improvement was also significant in patients across all risk, high-risk, or low-risk disease. Dr. Neeraj Agarwal: So, Jeanny, this is great news. So, the main message from this abstract for our audience is that triplet therapy of darolutamide plus docetaxel plus ADT is more efficacious than the doublet of ADT plus docetaxel chemotherapy, regardless of disease volume or risk status. One important caveat I would like to note is that triplet therapy with the darolutamide was not compared with the doublet therapy of ADT plus darolutamide or any androgen receptor signaling inhibitor such as abiraterone or apalutamide or enzalutamide, all of which have shown benefit consistently, regardless of volume status, and in the case of abiraterone, also in the context of high-risk disease setting, as we saw in the LATITUDE trial. Dr. Jeanny Aragon-Ching: Absolutely. I agree with that, Neeraj. Those are important points to consider. Now, moving on to a different setting in prostate cancer across the disease continuum, let's discuss Abstract 18, titled “Rucaparib for Metastatic Castrate-Resistant Prostate Cancer.” This is TRITON3 entering overall survival and efficacy of rucaparib versus docetaxel or second-generation engine pathway inhibitor therapy, which will provide us with some additional data regarding overall survival. Neeraj, based on this new abstract, can you tell us more about TRITON3, which will be presented by Dr. Alan Bryce and colleagues from the Mayo Clinic Arizona? Dr. Neeraj Agarwal: Of course. So TRITON3 is a randomized multicenter open-label phase 3 trial where rucaparib was compared with the physician choice of docetaxel chemotherapy or abiraterone or enzalutamide in those patients who had not received chemotherapy in the metastatic castration-resistant prostate cancer setting, and they had to be progressing on a prior androgen receptor signaling inhibitor in any setting prior. So, they just had to have disease progression either in the hormone-sensitive setting or CRPC setting on one of the AR inhibitors, and they had to have a BRCA1, BRCA2, or ATM alteration. So, in this context, these patients were randomized to rucaparib versus physician's choice of agent, which could again be docetaxel chemotherapy, abiraterone, or enzalutamide. So, OS maturity is 54% in BRCA group and 59% in the intention to treat population. In BRCA1 and BRCA2 populations, radiographic PFS, which was the primary endpoint, was 11.2 months in rucaparib group and 6.4 months in the physician choice arm. In the intention to treat population where you include all patients BRCA plus ATM patients, ATM positive patients. Radiographic PFS was 10 months almost versus 6.4 months with standard of care. And both were statistically significant as well as clinically meaningful improvement in the radiographic progression-free survival with rucaparib over physician's choice of either docetaxel or enzalutamide, or abiraterone. I would like to note that most frequent toxicity which we see with this group of agents is most frequent grade III or more toxicity was anemia, which was present in approximately 24% patients treated with rucaparib. Dr. Jeanny Aragon-Ching: Yeah. This is a really exciting update, Neeraj. What do you think is the key takeaway from this abstract? Dr. Neeraj Agarwal: The key takeaway is that TRITON3 trial met its primary endpoint, and rucaparib significantly improves radiographic progression-free survival in BRCA mutation-positive patients or BRCA ATM-positive patients. Overall survival is still immature, and these results further establish rucaparib as one of the standard of care options in those patients who have metastatic CRPC with prior treatment with the AR signaling inhibitor and who harbor one of the BRCA mutations or BRCA NAT mutations. So, Jeanny, before moving on to the renal cell carcinoma section in this podcast, there is an Abstract in prostate cancer talking about correlation between the source of funding and disparities among patients with advanced prostate cancer. So, I'm referring to that Abstract 40, titled “Source of Funding and Enrollment Disparity in Prostate Cancer Clinical Trials.” I thought this was an interesting abstract. Could you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in Abstract 40, Dr. Riaz and Dr. Bryce, and colleagues actually looked at phase II and III clinical trials that involved prostate cancer patients that reported on patients with age by 65 years, and they got the data from the MEDLINE and Embase databases. Trials recruiting from the United States were considered eligible for analysis by race and ethnicity. So, in terms of race and ethnic enrollment, they found that black patients were significantly underrepresented in the industry's funded trials. Notably, no significant disparity was observed in the US government-funded trials, but Hispanics were also significantly underrepresented in industry-funded clinical trials. However, no significant disparity was seen in terms of older adults overall and by funding sources. Remarkably, Black patients' representation in industry-funded prostate cancer trials has actually decreased over the last three decades. Dr. Neeraj Agarwal: That's concerning. So, what is your key takeaway from this trial, Jeanny? Dr. Jeanny Aragon-Ching: The key message here is that Black and Hispanic men with prostate cancer are significantly less likely to be included in industry-sponsored clinical trials. A bigger concern is that black patients' representation actually continues to decline over time. So these results warrant a really more proactive role by regulatory bodies to ensure that a proportional representation of minorities in the industry trials, which in turn will make these results more applicable to a wider entire population of men with prostate cancer. Dr. Neeraj Agarwal: Thanks, Jeanny. Let's move on to renal cell carcinoma. I saw some innovative research correlating the efficacy of immune checkpoint inhibitors with the time of the day these checkpoint inhibitors were administered. So, interestingly, there were two studies from two different groups of investigators showing very similar results. Please tell us about this innovative research correlating outcomes with immune checkpoint inhibitors with the time of the day these medicines or these drugs were infused into the patients. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. I think they're very exciting and interesting. So there's actually two abstracts, so Abstract 681 and 678, which we, of course, can discuss separately. So, let's probably start first with Abstract 678. Neeraj, do you want to explain to us further about this abstract? Dr. Neeraj Agarwal: Yes. When our center participated in that abstract, which was led by Dr. Nazli Dizman from Yale University, Dr. Dizman and colleagues examined the relationship between the time of the administration of immune checkpoint inhibitors, or ICIs, as we call them, during the time of the day, and outcomes in patients with metastatic renal cell carcinoma. So, I'd like to point out that previously Dr. Qian and colleagues reported an association between the time of day of immunotherapy infusion and survival outcomes in patients with metastatic melanoma. In this study, Dr. Dizman and colleagues, which included our center also, patients with metastatic RCC who received nivolumab with or without ipilimumab– so these patients all received either nivolumab alone or without ipilimumab. And patients who received less than 25% of infusion after 4:30 pm. were assigned to the early-time of infusion group. So, if they have received less than 25% infusion of these immunotherapies after 04:30 pm in the evening, they belong to the early infusion group, and the rest were assigned to the late infusion group. In the univariate analysis, numerically higher objective responses and time to treatment failure were observed in the early infusion group compared to the late infusion group. So, differences were 33% versus 25% in objective responses in early versus late infusion group. If you look at time to treatment failure, 8.3 months versus 4.4 months in early versus late infusion group. In the multivariate models, which took into account the clinical characteristics such as age, gender, line of treatment, IMDC risk category, histological subtypes, there was a trend towards improved outcomes in those who received these infusions with ICIs early in the day. So, Dr. Dizman concluded that larger randomized and controlled investigations are warranted to examine the impact of this chronal modulation, if you will, on the efficacy of immune checkpoint inhibitors in metastatic RCC sets. Dr. Jeanny Aragon-Ching: Yeah, this is very interesting data, Neeraj. And that actually resonates closely with this other abstract by Fernandez Manias and colleagues in Abstract 681. So, in this abstract, the primary outcome was overall survival, but they did look at other secondary endpoints like time on treatment, time to the next treatment, and overall response rates. Now, because of the small number of events, the authors actually focused on just patients who received second-line immune checkpoint inhibitors. And what they did was they looked at patients who received overall more than 20% of their infusions after 04:30 pm, and they found that those who did receive actually fewer infusions had a significantly shorter time on treatment and had a worse overall survival. And similar results were seen when they looked at those who got more than 50% of their dose of checkpoint inhibitors that were administered after 04:30 pm, so interestingly enough, there was a 16% increase in the risk of death for each 10% increment of checkpoint infusion after 04:30 pm. So the key message here is that administration of checkpoint inhibitors after 04:30 pm is associated, unfortunately, with inferior outcomes. Now, these results should, of course, be further considered in the organization overall of the outpatient clinic as it can impact patient survival and outcomes. Dr. Neeraj Agarwal: Very interesting. So similar results from two independent groups of investigators from two different continents obviously made this research area very appealing and pertinent. Ideally, I think these results should be validated prospectively, but that will take time. But investigators who have already lagged multiple phase III trials should explore validating these results in the last phase 3 trials which have already been reported and where the data on the timing of infusion is available. Once validated, I think these results may profoundly influence how we organize, as you said, Jeanny, the outpatient scheduling of these checkpoint therapy infusions compared to those who are not checkpoint inhibitors. I think this is going to have very interesting data overall, no doubt. Before moving onto bladder cancer, I would like to discuss an important abstract related to testicular cancer patients titled “Longitudinal Evaluation of Plasma MicroRNA-371 to Detect Minimal Residual Disease and Early Relapse of Germ Cell Tumors.” Could you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this is a very interesting up-and-coming Abstract, it's number 407, which will be presented by Dr. Lucia Nappi and colleagues. In this study, clinical patients with stage I germ cell tumor with available plasma samples after they underwent radical orchiectomy were all included. So, they looked at sensitivity, specificity, negative, positive predictive values, an area under the curve in predicting tumor recurrence, and they evaluated the microRNA-371, I'll just call it and truncate it as miR-371, and compared the same operating characteristics of current gold standard diagnostic tests. Relapse-free survival was correlated to post-orchiectomy miR-371 status, which could be either positive or negative. So, at a median follow-up of 41 months, 101 patients with clinical stage one germ cell tumor were included. About 35% of them experienced a disease relapse during that time of follow-up. Now, what they found was miR-371 was positive in about 63% of the relapsed patients, and the miR-371 positivity preceded clinically evident disease by a median of about three months. The specificity and positive predictive values were 100%, sensitivity was like 63%, and negative predictive value was 83.5%, so very high. No false positive results were seen. And, the authors reported that the recurrence-free survival of the patients who had positive post-orchiectomy miR-371 was significantly shorter compared to those patients who had a negative biomarker for the miR-371. So, they concluded that the miR-371 sensitivity correlated with the tumor burden, time between tumor relapse, the microRNA testing, and histology. It was notably a little bit more sensitive in non-seminomas compared to those who had seminoma. Dr. Neeraj Agarwal: Interesting findings, indeed. So, Jeanny, what is the take-home message from this abstract? Dr. Jeanny Aragon-Ching: Yeah, so I think the key takeaway is that microRNA-371 seems to be a good test, like a biomarker for predicting disease relapse in patients with early-stage germ cell tumor. So, additionally, its high specificity and positive predictive value in predicting relapse could really be used and utilized to guide adjuvant therapy, selections, and decisions after orchiectomy. Further validation in other studies, such as swab 1823, are currently ongoing or planned to validate its clinical utility. So Neeraj, moving on to bladder cancer, the last abstract I'd like to mention before we wrap up the podcast is Abstract 563, titled “Utility of ctDNA in Predicting Outcome and Pathological Complete Response in Patients with Bladder Cancer as a Guide for Selective Bladder Preservation Strategies.” Neeraj, can you tell us more about this abstract? Dr. Neeraj Agarwal: Sure. So, this study was led by Dr. Lars Dyrskjøt. He and colleagues evaluated the prognostic value of circulating tumor DNA, or ctDNA, in predicting recurrence in a cohort of 68 patients with muscle-invasive bladder cancer who received new adjuvant chemotherapy prior to cystectomy. So ctDNA was analyzed two times at baseline before new adjuvant chemotherapy and then before surgery or before cystectomy. So, patients had ctDNA assessed before neoadjuvant chemotherapy and then before cystectomy after completion of new adjuvant chemotherapy. At baseline, of the 64 patients, around 60% were ctDNA negative, and 40% were positive for ctDNA. So of those patients who were ctDNA negative, 84% achieved pathologic complete response, while in those who tested ctDNA positive, only 35% achieved their pathologic complete response after surgery. Prior to surgery, 84% of patients were ctDNA negative, and 81% achieved pathologic complete response. While none of the ctDNA-positive patients who were positive before surgery and after neoadjuvant chemotherapy, none of them achieved pathologic complete response, which translates into a positive predictive value of 100% and a negative predictive value of 81% for this test. So based on both ctDNA time points, the probability of ctDNA negative patients to achieve a pathologic complete response was significantly higher than ctDNA positive patients. At a median follow-up of 59 months, ctDNA-positive patients without pathologic complete response demonstrated significantly lower recurrence-free survival and overall survival compared to those who were ctDNA negative. So, I want to repeat that, at a longer follow-up, which Dr. Dyrskjøt will be presenting, ctDNA positive patients without pathologic complete response had significantly lower recurrence-free survival and overall survival compared to ctDNA negative patients. Furthermore, ctDNA status at baseline, which is before neoadjuvant chemotherapy and before cystectomy, was a better predictor of recurrence-free survival compared to pathologic complete response, which is a remarkable finding here, although it's a smaller data set. Dr. Jeanny Aragon-Ching: Agree completely, Neeraj. So, I think the importance here, too, is upon prospective validation in larger data sets, we will find that a negative ctDNA test would help in identifying patients who can benefit more from bladder-sparing strategies. Neeraj, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Before I share my final thoughts, Jeanny, I would like to thank you for joining us and sharing your insights. I always find them very valuable. So, thank you so much for taking the time. I would like to wrap up the podcast by saying we are seeing an explosion in the development of novel therapeutic approaches for our patients with genitourinary cancers. At the 2023 ASCO GU meeting, we will have multiple studies with practice-impacting data presented by investigators from around the world. I urge our listeners to come and join us in the meeting not only to celebrate these successes but also to help disseminate these cutting-edge data to practitioners and maximize the benefit for our patients across the globe. I would like to thank our listeners for joining us today. You will find links to the abstracts which we discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you so much. Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:  Dr. Neeraj Agarwal @neerajaimms Dr. Jeanny Aragon-Ching Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures:  Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis  Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics  Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma 

united states university black guide dna medicine safety patients os trials phase funding pfizer hispanic yale university astrazeneca advances mir atm utility bayer notably abstract oncology combination merck efficacy relapse prostate cancer hispanics janssen new england journal novartis gleason agarwal latitude accommodations sanofi precision medicine asco genentech amgen brca bristol myers squibb adt takeda rcc brca1 pfs riaz bladder cancer brca2 nektar qian crpc microrna medline eisai icis ctdna emd serono jeanny aveo foundation medicine docetaxel mrcc asco gu seattle genetics mayo clinic arizona dendreon embase pharmacyclics janssen oncology transcript dr neeraj agarwal mei pharma astrazeneca medimmune

Developing the Next Generation of Prostate Cancer Researchers

Learning While Working Podcast

Play Episode Listen Later Nov 15, 2022 15:07

Dr. Charles Ryan, president and CEO of the Prostate Cancer Foundation (PCF), joins ASCO Daily News Editor-in-Chief Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute, to assess impactful prostate cancer research from the PCF's recent conference and discuss Dr. Ryan's vision for the future, including increasing access to cutting-edge care. TRANSCRIPT Dr. Neeraj Agarwal: Welcome, to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News, and director of the Genitourinary Cancers Program at the University of Utah Huntsman Cancer Institute. Today, we'll be discussing compelling research that was featured at the recent Prostate Cancer Foundation Scientific Retreat, and I'm very pleased to welcome Dr. Charles Ryan, the president, and CEO of the Prostate Cancer Foundation. Our full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the ASCO Daily News Podcast are available on our transcripts at: asco.org/podcasts. Dr. Ryan, thank you for taking the time to be with us today. Dr. Charles Ryan: Dr. Agarwal, thank you. It's my pleasure to be with you. Dr. Neeraj Agarwal: So, Dr. Ryan, before I discuss the PCF meeting, I would like to ask you, what made you move to the PCF as the president and CEO when you had a flourishing career as a division chief of a large academic program, and as one of the top and internationally recognized investigators in prostate cancer? Dr. Charles Ryan: Well, thanks. That's a fair question, I guess. And it took me about three minutes to make the decision when I was offered the position, simply because the Prostate Cancer Foundation has been one of my intellectual homes for my entire career. I've been at the University of Wisconsin, Memorial Sloan Kettering Cancer Center, UCSF, and the University of Minnesota, and all those institutions were affected by the Prostate Cancer Foundation, or previously, CaP CURE. So, I was involved in their research during my time at all those institutions. In addition to my own personal legacy with the PCF, but more importantly, is the fact that it is an organization that funds the deepest scientific inquiry into prostate cancer and the ways that it can cause suffering and death for men with the disease and has made tremendous progress in identifying factors that lead to that lethality. It's also a community of scholars, a community of researchers, that is a platform really for collaboration. And it's also an organization with a world reach - we fund research in 28 countries around the world, and we fund research going from the scope of very basic research to correlative research, to quality of life, and health services research. Dr. Neeraj Agarwal: That is truly impressive and inspiring. So, what is the mission of the Prostate Cancer Foundation formally? Dr. Charles Ryan: Formally, it's pretty simple. The mission of the Prostate Cancer Foundation is to reduce the death and suffering from prostate cancer. Dr. Neeraj Agarwal: So, the 29th PCF Scientific Retreat was recently held on October 27 to October 29th in Carlsbad, California. What were the goals and objectives of this meeting? Dr. Charles Ryan: The meeting, we call it the retreat, it's an annual event and it always has several goals. One is, it's where we announce and hand out, if you will, our awardees of our various awards that we give. It's also a reporting-in process where those who have been using PCF funding are called to come and discuss their work. We also want it to be an open forum for individuals to come and interact - it's really a collaboration and an interaction vehicle as much as anything. So, when you come to our scientific retreat, we all stay at the same hotel, we all share meals together, nobody goes out for dinner. You don't leave the campus, essentially, of the hotel where we are. We have many, many round tables set out, it's designed to be interactive. We have a big room where people are giving their talks, but if you step outside of the room, there are likely to be many, many conversations happening, and those conversations range from collaborations being formed to people looking for jobs, to people getting advice and mentoring, and even people sharing, as I've done over the years, compelling and challenging patient stories around prostate cancer, and really engaging in what communities do - which is, share ideals, share a mission, and share a passion for what they do. Dr. Neeraj Agarwal: Very interesting. Very inspiring. Please tell us some of the highlights of the meeting. Dr. Charles Ryan: Sure. Well, there are many highlights. There are many things happening in prostate cancer research. Most notably, there are a number of papers and investigators that are looking at how prostate cancer evolves, and probably the most significant set of observations that have been made in the field in the last decade, have been understanding the diverse and numerous mechanisms that underlie the evolution of prostate cancer from a disease that responds to hormonal manipulation, to one that becomes resistant to hormonal manipulation. And so, a lot of the work that's happening now is identifying, for example, the evolution of neuroendocrine prostate cancer, or mixed types of prostate cancer, or this sort of evolution of it under constant therapy. And that is allowing the exposure of new targets that we can exploit for new therapy development, and that feeds into some of the grant-making process that's going on in the background. And so, you have a lot of individuals who are looking at this or that mechanism pathway related to disease resistance that they can exploit, and whether they can create small molecules to do that, or antibodies to do that, et cetera. At the same time, we have a strong component of discussion of how prostate cancer affects different populations. So, we had some really nice talks looking at healthcare disparities and different populations across the world, and how they're affected by prostate cancer, and how care delivery may be impacted in those groups of patients. And then you have topics ranging around survivorship and other factors that are looking at what is life like for a man with advanced prostate cancer, which is in many cases, you know, men who get prostate cancer, who have recurrent disease, who end up going on systemic therapy are frequently on the treatment for 5, 10, 15 years. And so, survivorship, and how they live their life, and what the complications are of that treatment, is tremendously important because it's such a daily experience for these men undergoing treatment. Dr. Neeraj Agarwal: So, how does the Prostate Cancer Foundation support and build the next generation of prostate cancer researchers? Dr. Charles Ryan: Right. So, the PCF supports the next generation in a very specific way, in addition to the informal way of bringing people together and inducing collaborations. We have a program called the Young Investigator Program. It started formally in 2008, but before that, there were one-off, if you will, Young Investigator Awards being given. So, our Young Investigator Awardees receive $75,000 per year to support their work, and we awarded 34 of those this year. The range is somewhere from 25 to 34 per year. We get over 100 applications for them every year. It's a straightforward application - they need to have a project that's going to be about three years in length, they need to be mentored, and they are best served by describing a mentorship plan for themselves and how that mentorship relationship will help them grow in their careers. Now, once you become a Young Investigator, it's not that we just write you a check and wish you well, we do that, but we also have annual check-ins. So, we try to visit the sites of our Young Investigators, see them in their home institution, and meet with their colleagues and their mentors. And that's one of the things I do, or Howard Soule does-- Howard Soule, is our chief scientific officer, one of those things we try to do. We also bring them to the scientific retreat that we just had last week, and we have them present their data. So, a vast number of the individuals who are presenting at the scientific retreat are in fact, Young Investigators, or they were Young Investigators when they started the projects that they are presenting. And then, the other thing we do is we have another retreat specifically for the Young Investigators, and that's called the Coffey-Holden Retreat, and that's named after Don Coffey, the late researcher from Johns Hopkins, who is really considered to be one of the grandfathers of prostate cancer research, and Stuart or Skip Holden, who is one of the founders of the Prostate Cancer Foundation, and a urologist at UCLA. So, that event that we do is designed for people to come to give highlights of the work that they're doing; it's designed to be incredibly interactive. In fact, we have 15 or so minutes of presentation, followed by sometimes 25 minutes of questions for each presenter. There's always a line of people who are waiting to ask questions, and it's designed to engage and have that dialogue with the Young Investigators, to make their science better, and to get it known. And so, the Young Investigator Program, it's about 30 individuals per year on average, and the average age is about 30. Many of these are postdoctoral PhDs, and many of them are fellows, or early-stage faculty, MDs. And I like to think that if somebody's going to work until the age of 70, we're stimulating, or launching a 40-year career with these Young Investigator awards. So, I like to think that if we give 25 out, times 40 years, that's 1,000 years of research that we're sort of stimulating with this Young Investigator program. And I bring that up for the reason that we're very proud of the fact that many of our Young Investigators may start out in prostate cancer, and their ideas, their science, takes them elsewhere. And that's what science does. And we, of course, are very, very focused on solving the problem of prostate cancer, and we want people to do that. But we also understand that by launching a scientist, by launching a scientific career, you may end up with people going off in different directions. And so, we have many examples of that. And in my talk this year, I actually highlighted a person who, let's say she won an investigator award when she was young, it was before the formal Young Investigator Award was named, and this was a person who is creating conjugates for the delivery of chemotherapy to prostate cancer cells. And this was Carolyn Bertozzi up at UC Berkeley, and she just won the Nobel Prize. She didn't win the Nobel Prize for research she did on prostate cancer, but at some point, at one point in her career, this was a direction she was going, and she got two grants from us in 1999 and 2000, that helped her work continue on and go the direction that it did. Dr. Neeraj Agarwal: Yeah. And congratulations. Dr. Charles Ryan: Sure. I'll take credit for that one. Dr. Neeraj Agarwal: Being the President and the CEO, you deserve the credit. Dr. Charles Ryan: Sure. That's my job. Dr. Neeraj Agarwal: So, we are coming to the end of the interview, but let me ask you this; the prostate cancer field is so constantly evolving. What is your vision for PCF going forward? Dr. Charles Ryan: Well, my vision for the organization is that we are going to continue on our mission to reduce the death and suffering from prostate cancer. But that's a fairly general statement, and one of the ways you can do that is you can research cancer at a molecular level, and you could try to develop new therapies - we're going to continue to do that. But there's also a real problem, especially, in the United States, and actually globally, with individuals with prostate cancer who are not receiving the cutting-edge care, not receiving the cutting-edge therapy. We have some data that in the United States, maybe upwards of 50% of men with metastatic hormone-sensitive prostate cancer are not getting the therapies that are supported by the latest findings from randomized phase III trials. And this may be for economic reasons, it may be communications or an education deficit with their treating clinicians, and there may be other factors as well. So, as we think about the vision of this, we need to be mindful of that, because if we only focus on studying the cancer molecularly, and we don't address what's happening on the other end, then we're not completing the story, and we're not completing the mission. And so, I've started calling Prostate Cancer Foundation the Global Public Square of Prostate Cancer, because I think of four sides of that square - funding research, as of what we just got done talking about, education and communication, is another one, and we do that in the same way that you are doing this today - through podcasts, and web content, and in-person meetings, as well as applied discovery, which is helping our researchers take their discoveries or their findings out into the clinic. Now, you might think, "Well, that's a small molecule, becoming a company going into a phase I clinical trial." Certainly, that's part of it, but it's also the epidemiologist who is making observations about diet and exercise, who is then empowered to do a clinical trial of exercise and diet intervention. It's also the health services researcher who is able to use their data to go talk to payers or talk to organizations about how care may be delivered differently. So, that's applied discovery. And then finally, supporting the patient is part of what we do. So, we also hold patient webinars every month, we've held patient summits at various points around the country where we bring patients together and talk to them about the latest research or about the factors we've discussed, such as survivorship, or quality of life after treatment, or treatment complications, and things like that. Dr. Neeraj Agarwal: That's wonderful. Thank you so much for sharing your insights. Any final remarks, Dr. Ryan? Dr. Charles Ryan: Dr. Agarwal, thank you so much. It's always a pleasure to speak to another Genitourinary Oncologist, of course, about the field, and the opportunity to talk about the Prostate Cancer Foundation and what we're doing, and the directions we are trying to grow. We've had a great collaboration with ASCO over the years, and I hope that that continues as well. I hope anybody who is interested would come and visit us at: pcf.org, and they can also check us out on: urotoday.com, where we have a lot of content that might be of interest to them. Dr. Neeraj Agarwal: Thank you, Dr. Ryan, for taking the time to be with us on the ASCO Daily News Podcast today. And thank you to our listeners for joining us today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe, wherever you get your podcast. Thank you very much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy, should not be construed as an ASCO endorsement. Follow today's Speakers: Dr. Neeraj Agarwal @neerajaimms Dr. Charles Ryan @charlesryanmd Want more related content? Listen to our podcast on therapeutic advances in prostate cancer and other GU cancers. Advances in Genitourinary Cancers at #ASCO22 Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, Gilead Sciences Research Funding (Inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck , Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Charles Ryan: Honoraria: Janssen Oncology, Bayer Consulting or Advisory Role: Bayer, Dendreon, AAA, Myovant Sciences, Roivant, Clovis Oncology

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Training Frontline Leaders as Learning Accelerators with Ray Jimenez

Play Episode Listen Later Sep 9, 2022 29:12

About Ray Jimenez Ray Jimenez Ph.D. is the Chief Learning Architect at Vignettes Learning, trainingmagnetwork.com and situationexpert.com. He has worked with the American Bankers Association, Neiman Marcus, the US Air Force, NASA, Blue Cross, Goodwill Industries, Pixar Studios, Edison Missing Group, Dendreon, Netafim, Progressive Insurance, Bridgepoint Education, and the California Institute of Technology among others. Ray's expertise is in microlearning, story-based learning design, scenario-based learning design and creative problem solving. Key takeaways:The frontline leader is someone who coaches and troubleshoots on the job. Ray explains that workers need to focus on developing their skills in troubleshooting and thinking on the spot. Frontline workers day-to-day experience unpredictable environments and unique problems, so we need to empower them to think more.The most important tool is to have a dynamic thinking process for every worker – it's not about having all the answers. This redefines what we mean by working, which is about facing constant trial and error and discovering solutions. By applying tools like consequence thinking, learning becomes a natural byproduct.The role of assessments. Ray questions why there needs to be formal assessments alongside the learning process. It's natural to assess and recalibrate all the time, so assessment becomes a built-in process. It's not about proving your knowledge to anyone, it's there to demonstrate if something is working or not working.Segmented time stamps:(02:46) What is a frontline leader and how they can become learning accelerators(07:58) Why Ray is focusing on the frontline worker(11:56) Some tools to help frontline managers become learning accelerators(16:58) Informal versus formal learning(18:56) The role of L&D in this new way of workplace learning(22:05) Rethinking the role of assessmentLinks from the podcast:Visit Ray's WebsiteConnect with Ray on TwitterCheck out Situation ExpertRead ‘25 Thinking Tools'Listen to our previous interview with Ray Jimenez Sign up to Training Frontline Leaders as Learning Accelerators

Season 2| China: Hong Tang on Traditional Chinese Medicine and Targeted Cancer Supportive Therapy

Behind Biotech

Play Episode Listen Later Aug 3, 2022 32:17

Hong Tang Biography Dr. Hong Tang is Chief Medical Officer, and co-founder of OnQuality Pharmaceuticals. Hong is a Board-certified internal medicine physician with more than 15 years' experience in both drug development and medical affairs, and conducted all phases of clinical trials. She served as VP, Executive Medical Director, Medical Director, and Medical Officer in Dendreon, Juno, Astellas, BMS and NIH. OnQuality Pharmaceuticals is designing targeted cancer supportive care treatments aimed at preventing and treating the intolerable side effects caused by specific cancer drugs. Their mission is to make fighting cancer easier by alleviating the side effects of anti-cancer therapy, so the patients can continue cancer treatment and live with a better quality of life. OnQuality is based in Seattle and Shanghai. She received her medical degree in Traditional Chinese Medicine in Hefei, China, pursued her graduate study in Western medicine in Guangzhou, China, and at the University of Texas in San Antonio. She is also board certified in internal medicine and practiced as an internist in Indiana for almost 7 years. In this episode of Behind Biotech, we spoke with Hong about: Starting her career in Traditional Chinese Medicine, and how this education on holistic patient care influenced her career path The need for more targeted cancer supportive therapy, such as IL-6 inhibitors for CAR-T OnQuality's current pipeline in oncodermatology and oncogastroenterology

Hong Tang: Targeting the Common Side Effects of Cancer Therapies

Hopkins Biotech Podcast

Play Episode Listen Later Jun 30, 2022 26:14

Hong Tang is the co-founder and Chief Medical Officer of OnQuality Pharmaceuticals, a targeted cancer supportive care (TCSC) pharmaceutical company dedicated to the development of treatments to address specific side effects of cancer therapies- to improve the quality of life and outcomes for patients fighting cancer. Prior to founding OnQuality, she worked as a Physician-Scientist in numerous medical affairs and leadership roles at the NIH, Bristol-Myers Squibb, Astellas Pharma, Dendreon, and Juno Therapeutics. She studied medicine at Guangzhou University and studied pharmacology at the University of Texas-San Antonio. In this episode, we discuss OnQuality's clinical pipeline of TCSC drugs, the field of medical affairs, the inspiration we draw to pursue science and medicine, and the role of clinical conferences.Hosted by Joe Varriale.

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NBA Basketball Superstar Grant Hill Discusses Racial Disparities in Prostate Cancer

Cancer ABCs From Surviving To Thriving - How to Thrive with Cancer

Play Episode Listen Later Jun 9, 2022 27:51 Transcription Available

NBA superstar Grant Hill, also an Atlanta Hawks co-owner, and African American health advocate, has teamed up with Dendreon to combat the prostate cancer racial disparities experienced by African American men. He discusses, along with Cancer ABCs CEO Joel Nowak, how men, particularly African American men, can combat the disparities. They focus on how a man can develop their own playbook to beat prostate cancer, what role a man should play with his doctor and the importance of becoming an educated patient. Mr. Hill shared a program he has started with Dendreon called Start Strong. Start Strong (www.startstrong.us) is focused on raising awareness of the racial disparities in prostate cancer incidence and the importance of talking to your doctor about the best treatment options.Please note that during the interview, Mr. Hill provided the wrong web address for the Start Strong Program. The correct address is www.startstrong.us. Support the show

nba african americans superstar atlanta hawks blackhawks prostate cancer nba basketball racial disparities national basketball association grant hill start strong dendreon

Key Posters on Advances in GU Cancers at ASCO22

Play Episode Listen Later May 26, 2022 19:50

Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute. Transcript: Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcast. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study? Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.” So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria. Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics. So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588. Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics. The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset. Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues? Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers. Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.” Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract? Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy. However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma. The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States. Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute. Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract? Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings. So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics. Dr. Jeanny Aragon-Ching: Agree. Yeah. Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road. So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.” So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery. So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence. So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment. What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans. Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival. Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy. Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future. Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer. Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.” During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer. What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer. And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy. So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression. Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time. Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us? Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients. Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression. Dr. Jeanny Aragon-Ching: I agree with that. Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments. So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC. So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC. So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression. The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia. There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals. Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners? Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway. Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting. Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast expressed their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

united states university moving travel food speaker study cancer patients phase survival consulting fda pfizer psa forty drs absence gu astrazeneca advances bayer treated abstract oncology merck prostate cancer janssen calais novartis posters accommodations cancer care sanofi asco genentech amgen disclosures drug administration fda bristol myers squibb adt arches takeda characterization rcc pfs gilead sciences nature medicine ipi sparc nektar cbm hif eisai asco annual meeting jonathan rosenberg muc psma emd serono jeanny aveo foundation medicine vhl andrew armstrong ecog mrcc seattle genetics psma pet nyha dendreon pharmacyclics clinical program director arvinas janssen oncology mcspc neeraj agarwal toni choueiri mei pharma astrazeneca medimmune

ASCO Genitourinary Cancers Symposium, 2022: A Focus on Prostate Cancer

Play Episode Listen Later Mar 17, 2022 27:46

In this podcast, Dr. Alicia Morgans discusses recent data presented at the 2022 ASCO GU Cancers Symposium, including trials evaluating the use of first-line PARP inhibitors in combination with abiraterone for mCRPC, continuation of enzalutamide after progression, and imaging modalities as predictive and prognostic biomarkers. This activity is available for CE/CME credit. Claim your credit at pce.is/ascogu.Contributors: Dr Morgans has disclosed that she has received funds for research support from Atellas, AstraZeneca, Bayer, Myovant, and Pfizer, and consulting fees from AAA, Astellas, AstraZeneca, Bayer, Blue Earth, Clovis, Dendreon, Janssen, Lantheus, Merck, Myovant, Novartis, Pfizer, Sanofi, and Telix.Ms Martone has no relevant conflicts of interest to report.

claim pfizer aaa astrazeneca bayer merck prostate cancer janssen novartis sanofi asco parp martone astellas psma blue earth olaparib lutetium dendreon abiraterone genitourinary cancers symposium lantheus

Advanced Urothelial Cancer: Applying New Therapeutic Options, Part 2

Play Episode Listen Later Feb 11, 2022 37:03

In this second of two podcasts, discuss the management of advanced urothelial cancer with novel therapies and how to address adverse events, and concludes the episode with a review of audience questions and patient cases. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Arjun Balar, MDRana R. McKay, MDTerran W. Sims, MSN, ACNP-C, CNN-BC, COCNDr Balar: consulting fees: Bristol-Myers Squibb, Incyte, Istari Oncology, Janssen, Pfizer; consulting fees/research support: Immunomedics, Seagen; consulting fees/contracted research/fees for non-CME/CE services: AstraZeneca/Medimmune, Genentech; Merck; consulting fees/contracted research: Immunomedics/Gilead, Nektar, Seagen; consulting/ownership interest: EpiVax Oncology, GT Biopharma.Dr McKay: consulting fees: AstraZeneca, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novarits, Sanofi, Sorrento Therapeutics; Vividion Therapeutics; consulting fees/contracted research: Bayer, Pfizer, Tempus.Ms Sims: consulting fees: Coloplast.

cancer options claim pfizer sims astrazeneca therapeutic msn mckay merck janssen chemotherapy immunotherapy sanofi genentech bristol myers squibb tempus caris nektar gigu pembrolizumab seagen nivolumab ctdna incyte cme/ce coloplast atezolizumab arjun balar dendreon astrazeneca medimmune

The New Array of Choices in Prostate Cancer—What's Best for Your Patients? Part 1

Play Episode Listen Later Feb 10, 2022 30:30

In this first of two podcasts, Dr. Rana R. McKay discusses the optimal treatment selection and management of adverse events for patients with metastatic and nonmetastatic castration-sensitive prostate cancer (CRPC), including the use of taxanes, androgen receptor agonists, and other therapies.This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Arjun Balar, MDRana R. McKay, MDTerran W. Sims, MSN, ACNP-C, CNN-BC, COCNDr Balar: consulting fees: Bristol-Myers Squibb, Incyte, Istari Oncology, Janssen, Pfizer; consulting fees/research support: Immunomedics, Seagen; consulting fees/contracted research/fees for non-CME/CE services: AstraZeneca/Medimmune, Genentech; Merck; consulting fees/contracted research: Immunomedics/Gilead, Nektar, Seagen; consulting/ownership interest: EpiVax Oncology, GT Biopharma.Dr McKay: consulting fees: AstraZeneca, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novarits, Sanofi, Sorrento Therapeutics; Vividion Therapeutics; consulting fees/contracted research: Bayer, Pfizer, Tempus.Ms Sims: consulting fees: Coloplast.

patients choices claim pfizer sims astrazeneca msn mckay merck prostate cancer janssen array sanofi genentech bristol myers squibb tempus caris nektar crpc gigu seagen incyte cme/ce coloplast olaparib cspc abiraterone dendreon astrazeneca medimmune

The New Array of Choices in Prostate Cancer—What's Best for Your Patients? Part 2

Play Episode Listen Later Feb 10, 2022 30:40

In this second of two podcasts, Rana R. McKay, MD, and Arjun Balar, MD, and moderator Terran W. Sims, MSN, ACNP-C, CNN-BC, COCN, discuss the optimal treatment selection and management of adverse events for patients with metastatic and nonmetastatic castration-resistant or castration-sensitive prostate cancers, including the use of taxanes, androgen receptor agonists, and other therapies.This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributor:Arjun Balar, MDRana R. McKay, MDTerran W. Sims, MSN, ACNP-C, CNN-BC, COCNDr Balar: consulting fees: Bristol-Myers Squibb, Incyte, Istari Oncology, Janssen, Pfizer; consulting fees/research support: Immunomedics, Seagen; consulting fees/contracted research/fees for non-CME/CE services: AstraZeneca/Medimmune, Genentech; Merck; consulting fees/contracted research: Immunomedics/Gilead, Nektar, Seagen; consulting/ownership interest: EpiVax Oncology, GT Biopharma.Dr McKay: consulting fees: AstraZeneca, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novarits, Sanofi, Sorrento Therapeutics; Vividion Therapeutics; consulting fees/contracted research: Bayer, Pfizer, Tempus.Ms Sims: consulting fees: Coloplast.

patients md choices claim pfizer sims astrazeneca msn mckay merck prostate cancer janssen array sanofi genentech bristol myers squibb tempus caris nektar crpc gigu seagen incyte cme/ce coloplast olaparib arjun balar cspc abiraterone dendreon astrazeneca medimmune

Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC

The BioProcess Insider Expression Platform

Play Episode Listen Later Nov 18, 2021 12:52

Guest host Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah Huntsman Cancer Institute, interviews Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, on the practice-changing VISION trial and its impact on the current treatment paradigm for mCRPC. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,   Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,   AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas  Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,   Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,   AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas  Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,   Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,   AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas  Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

university vision utah new orleans trial patients ucla fda pfizer fatigue fusion astrazeneca bayer oncology merck johnson johnson prostate cancer ucsf janssen cancer research new england journal novartis accommodations cancer care sanofi asco genentech amgen glaxosmithkline abbvie bristol myers squibb takeda unitedhealth group cardinal health gilead sciences nektar improving care eisai psma huntsman cancer institute myriad genetics invitae emd serono aveo foundation medicine bavarian nordic seattle genetics psma pet lutetium dendreon pharmacyclics arvinas janssen oncology disclosures dr neeraj agarwal mei pharma endocyte

Dendreon‘s leap into the cell therapy CDMO space

Play Episode Listen Later Nov 5, 2021 27:21

Dendreon, a pioneer in the cell therapy space through its commercial product Provenge, has relaunched itself as a contract development and manufacturing organization (CDMO). BioProcess Insider speaks with Maria Cho, the VP of Business Development and Corporate Strategy, about Dendreon's strategic growth efforts in the cellular immunotherapy space and how it is embracing its proven success in the field to support others.

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Discover the Difference with Phil Dana

Discover the Difference

Play Episode Listen Later Sep 29, 2021 42:32

On our Discover the Difference podcast, Phil Dana from Dendreon shares his vision for how HR organizations will run in the future. He has worked with companies like Amazon and Intuit to understand organizational needs and aspirations and then reverse engineers what the talent pool needs to be through a combination of recruiting and professional development. Enjoy listening to our 7th episode.A CUENTO Production

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#23. Dendreon's Head of Human Resources Phil Dana: Cultivating Purpose Within Your Team

The Savage Leader Podcast

Play Episode Listen Later Sep 1, 2021 37:26

In this episode, Darren Reinke chats with Phil Dana, Head of Human Resources at Dendreon. Phil shares how the lessons he learned in the military and in construction have benefited him in his HR career, the importance of cultivating purpose within your team and organization, and why he intentionally surrounds himself with those smarter than him. Dendreon is a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy. Dendreon's flagship product, PROVENGE, was the first FDA-approved immunotherapy made from a patient's own immune cells. More than 40,000 men with advanced prostate cancer have been prescribed PROVENGE in the U.S. since 2010. Show Notes:How Phil Ventured from the Navy Into Human Resources [1:06]How the Perception of HR Has Evolved Over Time [4:01]Why People and Culture Are Having Major Implications on Business Strategy [6:39]How Phil Creates a Thriving Culture in a Less Structured Environment [8:07]Why Creating an Authentic True North Serves as an Anchor for Your Company [10:38]The Key Steps Phil Takes to Create Individualized Purpose Within His Team [12:49]How You Can Create Your Own Sense of Purpose Regardless of Occupation [17:18]Why You Should Instill the Mindset of Lifelong Learning Within Your Team [20:19]Why Phil Enjoys Being the Dumbest Guy in the Room [22:53]The Crucial Skillsets Phil Looks for Before Making a Hiring Decision [26:32]How Phil Evaluates Peoples' Team Ability and the Importance of Hard Work [30:07] Links:Phil's LinkedIn: https://www.linkedin.com/in/militarytalent/Dendreon's LinkedIn: https://www.linkedin.com/company/dendreon/

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OnQuality Pharmaceuticals - Phase 2 Cancer Supportive Care Therapy For Hand Foot Skin Reaction

Health Professional Radio - Podcast 454422

Play Episode Listen Later Jul 1, 2021 9:35

Dr. Michael McCullar, CEO, and Dr. Hong Tang, Chief Medical Officer at OnQuality Pharmaceuticals, a clinical stage pharma company pioneering the discovery and development of targeted cancer supportive care therapies that address cancer treatment-related toxicities at the molecular level, discuss the company's lead pipeline candidate, OQL011, the first targeted treatment for the severe cancer med side effect Hand Foot Skin Reaction (HFSR). OQL011 is currently in Phase 2 study at onco-dermatology clinics across the country. It is a topical ointment that can be applied to the hands and feet, acting locally to restore VEGFR signaling while avoiding any interference with the main cancer med mechanism of action. Michael McCullar is the Chief Executive Officer of OnQuality Pharmaceuticals. He has more than 20 years of pharmaceutical experience in strategic planning and development, drug discovery and operation, business development and commercial operation. Previously he served as Chief Operating Officer at Tolero Pharmaceuticals, where he oversaw drug discovery and development activities as well as corporate development, and commercial planning. He played a major role in the acquisition of Tolero by Sumitomo Dainippon Pharma for $780M ($200M upfront). Prior to joining Tolero Pharmaceuticals, he held multiple roles at Astex Pharmaceuticals including Senior Vice President of Business Development where he was involved in the acquisition of Astex Pharmaceuticals by Otsuka for $886M in cash. In addition, he served as Vice President of Development and Operations and led the FDA approval of Dacogen for the treatment of MDS, while at SuperGen, Inc. Dr. McCullar earned a PhD from the University of California and an MBA from the W.P. Carey School of Business, Arizona State University. Dr. Hong Tang, Chief Medical Officer, and co-founder of OnQuality Pharmaceuticals. Hong is a Board-certified physician with more than 15 years' experience in both drug development and medical affairs, and conducted all phases of clinical trials. She served as VP, Executive Medical Director, Medical Director, and Medical Officer in Dendreon, Juno, Astellas, BMS and NIH. #OnQualityPharmaceuticals #OQL011

Building Company Culture with Philip Dana Head of HR at Dendreon

AllVoices, Reimagining Company Culture

Play Episode Listen Later Jun 18, 2021 23:17

Welcome to Reimagining Company Culture, a series discussing emerging trends and priorities shaping the future of workplace culture and employee wellbeing. We highlight thought leaders who are constantly evolving their strategy and can provide insight to folks about how to address new business challenges. AllVoices is on a mission to create safe, happy, and healthy workplaces for all, and we're excited to learn from experts who share our mission.In this episode of Reimagining Company Culture, we're chatting with Philip Dana, Head of HR at Dendreon. Philip is an HR executive with a record of building high-performing teams within domestic and global Fortune companies and in “Great Place to Work” environments.About AllVoicesIn today's workforce, people often don't feel empowered to speak up and voice their opinions about workplace issues, including harassment, bias, and other culture issues. This prevents company leadership from making necessary changes, and prevents people from feeling fulfilled, recognized, and included at work. At AllVoices, we want to change that by providing a completely safe, anonymous way for people to report issues directly to company leaders. This allows company leadership real transparency into what's happening in their companies—and the motivation to address issues quickly. Our goal is to help create safer, more inclusive companies.To learn more about AllVoices visit us at www.allvoices.co!

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Ep 036: Phil Dana: Talent Acquisitions & Career Transition You Can't Teach Character

Workplace Warrior®

Play Episode Listen Later Mar 21, 2021 38:21

About Phil Dana: Philip Dana is an HR Leader who brings calm to the chaos, thriving on transformation and growth. He has been with companies like Amazon, Intuit, life technologies, and others. He says he has seen the worst and the best of humanity, sometimes standing right next to each other. Today, Phil is the Head of Human Resources for Dendreon Pharmaceuticals, an organization that is known for its prostate cancer treatments. He has a family that has battled cancer in its various forms, so he is excited to be a part of a team that fights back. Previously, he was the head of people operations for the Honor Foundation, a non-profit organization which helps Special Operations Forces like the NAVY SEALs and the Marine Raiders transition to civilian life. Phil describes himself as a data driven HR / People & Culture leader. He says he leverages his Irish DNA, Asia / Pacific-Northwest upbringing, military service as both enlisted & an officer and his experience at various corporations building teams to achieve peak performance. In this episode, Jordan and Phil discuss: Dendreon hired Phil as Head of Human Resources because of his commitment despite his lack of experience in the pharmaceuticals industry. Why former Navy SEALs and other Special Operations add so much value to corporations and organizations. The CEO's role in creating workplace equity and equality Key Takeaways: Your character and your “why” are more important than your technical knowledge if you show the discipline and passion to learn. Being passionate about what you do will make you both happier and more productive. During the transition, it is valuable to work with an advisor, mentor or coach to articulate who you are, what you stand for and how to frame your experience in the culture of the organizations you want to join. . "Lift the company culture to lift performance." — Phil Dana Mentioned: The Honor Foundation https://www.honor.org/ Get the complimentary guide: How To Select An Executive Coach at https://workplace-warrior-inc.mykajabi.com/selectcoach Get the Am I Abrasive Self Test at abrasive.workplacewarrior.com Connect with Phil Dana: Twitter: https://twitter.com/DendreonHR Facebook: http://facebook.com/philip.dana Email: philip.dana@dendreon.com pdana1548@gmail.com LinkedIn: https://www.linkedin.com/in/militarytalent?lipi=urn%3Ali%3Apage%3Ad_flagship3_profile_view_base_contact_details%3BAWfk3oegSridxLH24mBT3A%3D%3D Connect with Jordan: Get the complimentary guide: How To Select An Executive Coach at https://workplace-warrior-inc.mykajabi.com/selectcoach Get the Am I Abrasive Self Test at abrasive.workplacewarrior.com Website: www.workplacewarriorinc.com Twitter: https://twitter.com/jordangoldrich1 Facebook: https://www.facebook.com/jordan.goldrich Instagram: https://www.instagram.com/jordangoldrich/ LinkedIn: https://www.linkedin.com/in/jgoldrich/

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Episode 038: Beyond The Dollars - Towards A Meaningful Career In Pharmaceutical Sales With Pharmaceutical Sales Representative & Director, Derek Corson

Health Careers With Dr. Marn

Play Episode Listen Later Jan 27, 2021 50:24

Have you ever wondered how doctors and other healthcare providers stay current with the latest developments in therapies, medications, and medical devices? A lot of that information is conveyed through pharmaceutical sales representatives. A lot of you might not consider pharmaceutical sales as a healthcare career in itself, but the job entails a lot more than just making a hard sell. It is a sales representative’s job as well to educate healthcare providers on how their product can potentially help their patients. In this episode, Dr. Richard Marn brings in a friend of his to share about this and other aspects of the medical sales profession that we seldom hear about. Derek Corson is the Regional Sales Director for Dendreon’s North Atlantic arm. Before that, he spent the last 20 years hopping from pharmaceutical to medical device and then back again to pharmaceutical – all in search for a niche where he can make the most impact. Listen in and see if pharmaceutical sales and sales leadership could be one of the things on your list as a potential healthcare career.

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Prioritizing Care for Patients With Genitourinary Cancers Amid the Pandemic

Learning While Working Podcast

Play Episode Listen Later Nov 24, 2020 21:56

Jeanny Aragon-Ching, MD, FACP, a medical oncologist and clinical program director of genitourinary (GU) cancers at the Inova Schar Cancer Institute, shares her concerns over the decline in the screening, diagnosis, and treatment of prostate and other GU cancers amid the COVID-19 pandemic, and highlights promising clinical trials underway to advance the fields of prostate, bladder, and kidney cancers. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Jeanny Aragon-Ching, a medical oncologist who serves as the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. She joins me to discuss the worrying decline in screenings for prostate cancer due to the COVID-19 pandemic. Dr. Aragon-Ching also highlights clinical trials underway to advance the treatment of prostate, bladder, and kidney cancers. Dr. Aragon-Ching reports no conflicts of interest relating to the issues discussed in this podcast. And full disclosure relating to old episodes of the Daily News podcast are available on our transcripts at ASCO.org/podcasts. Dr. Aragon-Ching, it's great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Geraldine, for having me here. ASCO Daily News: Well, screening for prostate cancer is vitally important. What are your concerns about the long-term impact of delayed screenings, diagnosis, and treatment in this setting? Dr. Jeanny Aragon-Ching: Yes. So generally there have been already reports actually of observed decline in the common screening and diagnostic procedures and practices reflecting the impact of the COVID-19 pandemic on cancer prevention and early detection, signaling possible downstream effects on the timing and staging of future cancer diagnosis. Now, the issue is there has been no major guidelines or guidance regarding recommendations for screening during the pandemic. Now, one closely aligned guidance, if you will, from the NCCN, actually it's more for management, it suggests that patients with known low risk or certainly very low-risk prostate cancer may actually defer staging active surveillance or even testing for treatment until conditions are deemed safe. Therefore, determination of who really needs to be absolutely screened and certainly diagnosed, I think, is key. So especially since the subject of screening in prostate cancer has always actually been controversial even while the U.S. Preventive Services Task Force set forth the D recommendation, which is recommendation against PSA screening except for those target ages, let's say, between 55 and 69 years of age, they had a C recommendation, which involves individualized decision-making. And that means for us, we always have to have that dialogue with the patients in order to weigh the pros and cons of screening, especially during these times. So therefore, I mean, there's really no current standards that are set forth. A lot of it I think would be tailored to each individualized person and patient as well as physicians in practice during these times of pandemic. ASCO Daily News: Right. Well, COVID-19 will continue to be a threat for some time. So, how is the oncology care community to fill the gap in diagnostic services? Should cancer screenings, biopsies, and surgeries press on? If you see a patient that really needs treatment now, you, I assume, will proceed, correct? Dr. Jeanny Aragon-Ching: Correct. Yeah. Now, I do think the gaps in diagnostic services is really actually being remedied by performing other alternative services, if you will. So, for instance, remote telehealth services have gotten and gained ground since the COVID-19pandemic. And my general recommendation is, and the thinking really is minimal harm is really expected with delays in care certainly for certain types of risk of prostate cancer, or even bladder cancer or kidney cancers. If one were to delay the treatment for, let's say, 3 months, especially when we weigh the risk of mortality or morbidity from being exposed to COVID-19, I think those are the critical issues. Now, I would say that diagnosis and treatment for patients with GU cancers really require prioritization, adjustments for, let's say, screening biopsies, as well as individualized tailored approach to the diagnosis and treatment. The oncologic community, the GU community as a whole I think quickly filled that gap, as I mentioned earlier, by restricting non-urgent, in-person clinic visits, as well as adopting more remote telehealth visits to continue care that the physicians provide. So in terms of prioritization of the goals, patients, let's say, who need to undergo immediate diagnostic procedures and biopsies to make a diagnosis would be a priority. So especially for those who are deemed to have high-risk disease, for those who are likely to have high-grade disease, let's say, muscle-invasive bladder cancer, or let's say, big tumors that are seen on abdominal imaging for a renal cell cancer because we don't typically biopsy, let's say, renal masses to diagnose renal cell carcinoma. And as a general rule of thumb, procedures and treatments that are curative in intent would be considered high priority, whereas benefits of care from treatments certainly has to be weighed against a potential risk for infections and morbidity from COVID-19. Identifying the risks are important as well. So, for instance, treatment may be safely deferred for patients with low risk or certainly even intermediate-risk patients, whereas surgery may be delayed in most high-risk patients or alternative treatments, let's say, a neoadjuvant hormone therapy, coupled with external beam radiation, may be a treatment of choice with regard to the pandemic, and then may be a feasible alternative. So there's a lot of changes that are being set forth. Now with regard to radiation, there's also some concern, for instance, for lymphopenia, for those who undergo radiation. So actually identifying the patients who really would benefit from upfront treatment is key. So for patients with bladder cancer, let's say, who have muscle-invasive bladder cancer, they undergo surgery. We call it TURBT. And they undergo intravesical treatment. So a lot of it highly depends on the goal of the therapy. Is it curative in intent? Certainly if they undergo neoadjuvant chemotherapy, that adds to the layer of complexity for these patients because they are now being exposed to chemotherapy. But on the other hand, it is an important treatment with the goal of curative intent. And there's also something to be said about the varying institutional procedures. For instance, each institution has in place their own safeguards to screen, let's say, or treat patients with COVID-19. So in our institution, for instance, doing rapid COVID-19 tests to assess prior to performing these procedures, anesthesia or procedures that are high-risk for aerosolizing like respiratory secretions, would be of paramount importance. So I think there's a lot of institutional guidance also that comes into play in this day and age of COVID-19 in the treatment of our patients who have a diagnosis of GU cancers. ASCO Daily News: Absolutely. What can you tell us about new developments in diagnostics in the prostate cancer space which have truly advanced the field, resulting in fewer unnecessary biopsies and hopefully making men a little less reluctant to actually take care of their prostate health? Dr. Jeanny Aragon-Ching: Yes, that's a great question. And emerging data suggests that targeting using a combined MRI and an ultrasound fusion approach may perhaps increase the detection of significant high-risk prostate cancer, which, after all, is really the clinically significant and meaningful cancers that we need to treat, and therefore lead to perhaps lower detection of the lower risk prostate cancer that may not need to be treated. Now, it's important to recognize also that a negative MRI does not necessarily exclude the possibility of cancer. And therefore, biomarkers have been in place to be also helpful to perhaps avoid a biopsy in someone, let's say, who has a negative result. Now, there are numerous tests or biomarkers out there available. I always have said that a lot of times it is dealer's choice. It's highly dependent on what physicians are comfortable using, [and] what the availability is within their own institutions. And what the payers or insurance would pay for or cover. But there are several promising ones out there that help further predict if a patient has a high-risk of having a diagnosis of clinically significant prostate cancer. So, for instance, there was a urine base marker, it's called IntelliScore, so it looks at three different genes that would be able to discriminate a higher grade group of cancer versus a lower grade group. And that would help physicians and providers to help further define who needs to be biopsied, especially in this day and age, again, of COVID-19, so that they would be able to predict the likelihood of higher risk prostate cancer that ultimately needs to be treated. And that's not the only one out there that's currently available. There's other things like blood work or blood tests, like 4Kscore, which combines different parameters like free PSA, total PSA, intact PSA, that will help further predict high-grade prostate cancer. And the bottom line is all of these tests would help the physicians, the urologist hopefully to decide who they need to biopsy and prioritize versus those who can safely wait based on just an elevated PSA alone. ASCO Daily News: Well, African American men are at a significantly greater risk of getting prostate cancer. Can you talk about the health disparities that exist in this setting? And do you think the field is doing enough to address this? Dr. Jeanny Aragon-Ching: Mm-hmm. Yeah, so prostate cancer disparities actually constitutes one of the most complex issues in cancer today. So it is known that African American men unfortunately do have disproportionately higher incidence of prostate cancer, easily about 60% to 70% higher compared to Caucasian men counterparts. And they also have a higher 2-fold increased risk of prostate cancer death. So these are very relevant in the practice of prostate cancer in the field. African American men are also more likely to be diagnosed at a younger age. They tend to have more advanced and aggressive disease. And African genetic ancestry is really unfortunately not a modifiable risk factor, so when we talk about genetics...so there are potential reasons why this is so, why African American men may have a higher incidence or mortality. One potential explanation could be genetics. So it has been found that several genetic variants may be a little bit more common in African-American men. So, for instance, like 8q24 mutation in a tumor suppressor gene, there's differences in microRNA regulation, and they tend to, unfortunately, present with more aggressive tumors. And certain gene mutations also can lead to poor outcomes, let's say, P53 mutations, CDK M18, which is more commonly seen in African American men. Now, I would say that there are also possible issues with screening. So you may all recall that when US Preventive Services Task Force, which is felt to be the most influential in making recommendations for a PSA screening, gave a D recommendation in their most recent iteration of PSA screening, and that is that PSA screening is not recommended for the average person, especially for the older individuals, there was no real recommendation for men of African descent, or African American men. And they are really the ones who are underrepresented in these studies. So in one study, for instance, that looked at rigorous modeling, when they look at these trials, they suggested that PSA screening can actually yield greater mortality benefits for high-risk groups. And that includes men of African American descent. So one other big issue with this is probably access or utilization of health care, which would be a key factor in racial or ethnic disparities. And we know that standard prostate biopsies are still really the gold standard for diagnosis. And whenever we talk about better tools for making diagnosis, and we mentioned earlier about MRIs, for instance, MRIs may be less utilized in patients with lower, let's say, socioeconomic status. So there are a lot of reasons why we are seeing these disparities in men with African American descent. ASCO Daily News: So speaking of research, I'd love to ask you about your current research. You treat patients with bladder, kidney, prostate, and testicular cancers. Is there anything you'd like to highlight today? Dr. Jeanny Aragon-Ching: Yes. So, for instance, we are looking carefully at prostate cancer. And we are very much in tuned with the fact that a lot of men with prostate cancer have genetic variants and genetic and hereditary mutations. So we are looking carefully at the differences between men who present with de novo metastatic disease, and that means at the very first presentation to the medical or health professionals, they already have metastatic disease, versus those who were treated with curative intent treatment and then later on down the line present, unfortunately, with metastatic disease because they were not cured. We would like to further define what the differences is between these two population of patients because the former seems to, unfortunately, do worse. So those are the things that we are highlighting. In bladder cancer, we are very closely following what the outcomes would be for patients who have muscle-invasive bladder cancer. For the longest time, we've known that neoadjuvant chemotherapy followed by cystectomy is one of the gold standards of care for treatment of these patients. So the additional role of immunotherapy in addition to neoadjuvant chemotherapy, that is a key improvement perhaps in the field, especially now that we know that avelumab maintenance has been shown to improve survival for a lot of metastatic bladder cancer patients. And for kidney cancer, one of the key things that we would like to further highlight and improve upon the care is for patients who have high-risk, high-stage kidney cancers. So the standard of care remains to be surgery, but we know that a proportion of them would unfortunately recur with metastatic disease or have disease that comes back later on. So the idea is, can we improve upon these odds by giving them adjuvant therapy? So we have an adjuvant immunotherapy trial that seeks to answer this question of improvement in the [INAUDIBLE], in the metastases or recurrence for these patients who have or are deemed to have high risk disease (NCT03138512). ASCO Daily News: And what is the name of that trial? Dr. Jeanny Aragon-Ching: So this is actually CheckMate 914. This is the neoadjuvant immunotherapy nivolumab and ipilimumab versus a placebo. It's a placebo-controlled trial. ASCO Daily News: Excellent. So Dr. Aragon-Ching, is there anything else on your mind that you'd like to address today before we wrap up the podcast? Dr. Jeanny Aragon-Ching: Yeah. I really just think that the changes in practice brought on by the COVID-19 pandemic has us rethinking and reorganizing as an oncologic community the practice that we do. I believe that some are likely here to stay. So, for instance, the changes in the landscape and practices of treatment, we are really thinking about how long the duration of treatment are we providing. Even clinical trials, since the start of the pandemic, of course, the key issue here is some trials have closed their doors on enrollment. And I think we're starting to pick up on those. Some have limited its enrollment. And I think once we get institutional practices streamlined, and people are in general a little bit more comfortable about exposures because they see that everything is safe, I think we'll be getting back to our routine. But I don't think things are going to go back to the way they were. I think telehealth visits, for instance, are here to stay. We're creating a lot of guidance and guidelines on who are the patients who are best fit for these telehealth monitoring visits, or who are the patients who still need to come in person in order to get their care? ASCO Daily News: Absolutely. Well, Dr. Aragon-Ching, thank you so much for sharing your valuable insight with us today on the ASCO Daily News Podcast. Dr. Jeanny Aragon-Ching: Yeah. Thank you so much, too, Geraldine for having me and for sharing the insights with you all. ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. Jeanny Aragon-Ching Paid Honoraria: Bristol-Myers Squibb, EMD Serono, and Astellas Scientific and Medical Affairs Inc. Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, and Pfizer Speakers’ Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, and Astellas/Seattle Genetics Travel Paid or Reimbursed: Dendreon, Algeta/Bayer, Bristol Myers Squibb, and EMD Serono Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Using Scenarios to Transform your Virtual Classroom Sessions with Ray Jimenez

Play Episode Listen Later Sep 13, 2020 24:58

Scenarios are a powerful way to ensure your learning is performance focused. Using scenarios moves your online sessions away from being information dumps to being active and engaging experiences, where participants are sharing and problem solving together. One approach Ray talks about, is working with the group to bring out their experiences and basing the learning on those scenarios instead of fictional scenarios. About Ray JimenezRay Jimenez Ph.D. is the Chief Learning Architect at Vignettes Learning, trainingmagnetwork.com and situationexpert.com. He has worked with the American Bankers Association, Neiman Marcus, the US Air Force, NASA, Blue Cross, Goodwill Industries, Pixar Studios, Edison Missing Group, Dendreon, Netafim, Progressive Insurance, Bridgepoint Education, and the California Institute of Technology among others. Ray's expertise is in microlearning, story-based learning design, scenario-based learning design and creative problem solving. Links from the podcastFind out more about Vignettes LearningConnect with Ray Jimenez

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HR: Philip Dana, Head of HR for Dendreon talks HR during COVID.

The Business Talks Podcast

Play Episode Listen Later Sep 4, 2020 56:08

Philip Dana is the Head of HR for Dendreon. Dendreon is a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy. They are most notably known for their flagship product, PROVENGE which was the first FDA-approved immunotherapy made from a patient's own immune cells. This product is widely used for the treatment of prostate cancer. Phil has spent many years in HR and is an official member of the Forbes Human Resource Council. Thanks for listening and I hope you enjoy,Matt

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Episode 25: Phil Dana- Navy Veteran Head of Human Resources for Dendreon

The VeteranCrowd Spotlight

Play Episode Listen Later Aug 7, 2020 38:25

We placed the VeteranCrowd Spotlight on Phil Dana, a Navy Veteran recognized as a thought-leader on Networking and Transition. A family tradition... Philip Dana grew up in a family steeped in Navy tradition. Twenty members of his family have served in the Navy or Marine Corps. Phil's grandfather was a Marine wounded at the base of Mt. Suribachi during the invasion of Iwo Jima. His father served in both Korea and Vietnam. Dana grew up in the Philippines and other stations in the Pacific, and spent summers visiting his grandparents in the Pacific Northwest. Upon graduation from high school, Dana enlisted in the Navy, and served four years as an air crewman. He applied and was accepted to the US Naval Academy at Annapolis. He attended NAPS and became a surface warfare officer upon graduation in 1998. Dana has always sought entrepreneurial business opportunities, where process improvement and networking tools he has honed over the years could be best applied. Though he never envisioned a career in human resources, it became the natural fit. HIs military background and exposure to many in the special operations community led him to the Honor Foundation. The Honor Foundation a transition institute created exclusively for the U.S. Special Operations community. Phil served as a VP and “Chief of People Operations. Hiring veterans is a “natural sidecar” you get with Phil Dana. He is passionate about Navy Football and is a lifelong Seattle Seahawks fan. And Phil Dana currently serves as the Head of Human Resources for Dendreon, a commercial stage biopharmaceutical company delivering personalized immunotherapy treatments for Stage IV metastasized cancers. Dendreon's PROVENGE reprograms the body's own immune cells to detect and attack cancer cells, with little impact to healthy tissue or cells. A networking thought leader Phil Dana is a recognised subject matter expert on hiring and networking, and he has sound advice for veterans on transitioning and the do's and don'ts when building a professional network. He is a beast on LinkedIn, having developed disciplines and strategies that have grown his network with leaders and influencers everywhere. The Spotlight We placed Phil Dana in the Spotlight and he shared: Secrets of networking The art and science of using LinkedIn to become a thought leader Advice for transitioning veterans The proper way to build relationships, and what advice to ignore That 95% of opinions on Resumes are all wrong Veteran friendly business and avoiding patronizing The importance of mentors, sponsors, and candid feedback Executive coaches and the importance of reading You can follow Philip Dana on Linkedin and learn about Dendreon Immunotherapy https://www.linkedin.com/in/militarytalent/ And ask yourself, “Should I Join to the VeteranCrowd Network?” https://veterancrowdnetwork.com/contact/

Genomics Pioneer Who Travels The World To Discover Which Countries' Health Budgets Go The Furthest

Move the human story forward! ™ ideaXme

Play Episode Listen Later Jan 24, 2020 41:01

Ira Pastor, ideaXme exponential health ambassador, interviews Dr. William Haseltine, American biologist, entrepreneur and philanthropist, known for his groundbreaking work on HIV/AIDS and the human genome. https://www.amazon.com/Aging-Well-Solutions-Pressing-Challenges/dp/9811321639 Ira Pastor Comments: On today's show we have a thought leader who sits amongst a rare group of people who have been responsible for creating many aspects of the modern biopharma / genomics / regenerative medicine system as we know it today. Dr. William Haseltine: Routinely listed in major media sources as one of the world's most influential business people and most influential leaders in biotechnology, Dr. William Haseltine is an American biologist, entrepreneur and philanthropist, known for his groundbreaking work on HIV/AIDS and the human genome. Dr. Haseltine earned a PhD in Biophysics at Harvard University, where he worked under the direction of Dr. James Watson, co-discoverer of the structure of DNA, and Dr. Walter Gilbert, Nobel prize winner for developing DNA sequencing techniques. Dr. Haseltine was also a post-doctoral fellow in the laboratory of Dr. David Baltimore at MIT, where he worked on fundamental aspects of reproduction of retroviruses that are known to cause cancer in animals. Dr. Haseltine's Career He served for many years as a professor at Boston’s Dana Farber Cancer Institute, Harvard Medical School, and the Harvard School of Public Health. During his time at Harvard Medical School, he founded two major research departments working on both cancer and HIV/AIDS, as well as became a founder of several biotechnology companies including Cambridge Biosciences, The Virus Research Institute, ProScript, LeukoSite, Dendreon, Diversa, X-VAX, and Demetrix. In addition to all of that, he became extremely well known in the world of bio-pharma for his leadership as CEO of Human Genome Sciences (HGS), a company that truly pioneered the application of genomics to drug discovery. He is currently the president of the Haseltine Foundation for Science and the Arts, and is the founder, chairman, and president of ACCESS Health International, a not-for-profit organization dedicated to improving access to high quality health worldwide. Dr. Haseltine is the author of many books including: Modern Aging: A Practical Guide for Developers, Entrepreneurs, and Startups in the Silver Market; Aging with Dignity; Voices in Dementia Care; and Aging Well. On today's show we will hear from Dr. Haseltine: About his background and how he developed an interest in science, biology, and how after an amazing career in biopharma / genomics / regenerative medicine, why he is now so passionate about this new triad encompassing aging, dementia, and healthcare quality / outcomes. His history of ushering in the genomics era in big pharma. About his model of "Value-Based Care" essential for creating better health outcomes for older patients. His principle of “Optimal Aging” which is not just about health status, but about elderly people being able to live active, engaged, and productive lives. His learnings in regard to best practices in dementia care, observed around the globe, that should be adapted and adopted by healthcare systems, healthcare providers, and those loving and caring for a person with dementia. Credits: Ira Pastor interview video, text, and audio. Follow Ira Pastor on Twitter:@IraSamuelPastor If you liked this interview, be sure to check out ourinterview with Dr. Victor Dzau, President of the United States National Academy of Medicine and of the United States National Academy of Sciences! Follow ideaXme on Twitter:@ideaxm On Instagram:@ideaxme Find ideaXme across the internet including oniTunes,SoundCloud,Radio Public,TuneIn Radio,I Heart Radio, Google Podcasts, Spotify and more. ideaXme is a global podcast, creator series and mentor programme. Mission: Move the human story forward!™ ideaXme Ltd.

S3E12: Mitch Gold

What Fuels You

Play Episode Listen Later Sep 24, 2019 57:04

Mitch Gold, Co-founder, Executive Chairman and CEO of Alpine Immune Sciences and Managing Partner of Alpine BioVentures, talks about his lifelong commitment to helping patients with cancer, which stems from the loss of his mother when he was just four years old. Prior to his work at Alpine where they’re creating therapies to treat cancer and autoimmune disease, Mitch was the CEO of Dendreon, a biotech company that created a treatment for prostate cancer. Mitch discusses the lessons he learned at Dendreon, what he hopes to achieve with Alpine, what he loves about being a dad, and his interest in “where humanity is going.” This thought-provoking episode dives into the future of science, challenging yourself and those around you, and encouraging you to be a never-ending learner like he is.

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1: A Murder in Brentwood: Dr. Rachael Maidens

Southern Fried True Crime

Play Episode Listen Later Oct 17, 2017 39:51

a scandalous murder in one of the richest towns in Tennessee.Sources: https://www.southernfriedtruecrime.com/1-a-murder-in-brentwoodVoice Actors: Kayla C. as the bartender, Bethany T. as the ex-girlfriend, Kayla K. as the DA, Jamie Stevens as the Frisbie family lawyer, Stephen Burnette as the Dendreon employee and Shane Lowery as Randy MaidensWritten, hosted, produced by Erica KelleyResearched by Erica KelleyOriginal Graphic Art by Coley Horner Original Music by Rob Harrison-Gamma RadioMerch | Donate | In the Media:https://southernfriedtruecrime.com @southfriedtruth (Twitter) @southernfriedtruecrime (Insta)https://www.facebook.com/southernfriedtruecrimehttps://www.youtube.com/southernfriedtruecrime

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FirstWord Pharmaceutical News for Thursday, June 29 2017

Play Episode Listen Later Jun 29, 2017 1:52

Today in FirstWord:

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FirstWord Pharmaceutical News for Friday, February 6, 2015

Play Episode Listen Later Feb 6, 2015 1:44

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A Look at the Year That Was in Biotech

The Bio Report

Play Episode Listen Later Dec 24, 2014 15:15

The year 2014 was one for the record books for the biotech industry. In part one of a two-part podcast, we take a look back at the year that was with Adam Feuerstein, senior columnist for TheStreet.com. Feuerstein discusses the growing controversy over drug pricing, the newsmakers of 2014, and lessons from the Dendreon bankruptcy.

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FirstWord Pharmaceutical News for Tuesday, November 11, 2014

Play Episode Listen Later Nov 11, 2014 7:24

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FirstWord Pharmaceutical News for Wednesday, August 13, 2014

Play Episode Listen Later Aug 13, 2014 8:14

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FirstWord Pharmaceutical News for Tuesday, June 10, 2014

Play Episode Listen Later Jun 10, 2014 8:13

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FirstWord Pharmaceutical News for Monday, April 14, 2014

Play Episode Listen Later Apr 14, 2014 9:51

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FirstWord Pharmaceutical News for Wednesday, November 13, 2013

Play Episode Listen Later Nov 13, 2013 11:59

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FirstWord Pharmaceutical News for Monday, October 28, 2013

Play Episode Listen Later Oct 28, 2013 10:11

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FirstWord Pharmaceutical News for Wednesday, September 18, 2013

Play Episode Listen Later Sep 18, 2013 12:22

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FirstWord Pharmaceutical News for Friday, May 10, 2013