Podcasts about Androgen deprivation therapy

Dr. Hoffman continues his conversation with integrative urologist Dr. Geo Espinosa.

In this emergency episode of the Intelligent Medicine Podcast, Dr. Ronald Hoffman and integrative urologist Dr. Geo Espinosa discuss the recent announcement of former President Joe Biden's advanced prostate cancer diagnosis. They delve into the nuances of PSA testing, the implications of prostate cancer staging, and the treatments Biden may face. The conversation also highlights the importance of an integrative approach, including dietary recommendations, supplements, and exercise, to manage side effects and improve quality of life for patients undergoing androgen deprivation therapy. Dr. Espinosa shares his expertise on the subject and offers insights into managing advanced prostate cancer.

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As part of the 2024 Prostate Cancer Patient Conference, Dr. Eric Small reviews Androgen Deprivation Therapy, including choices of agents, side effects, considerations in timing, duration, intensity of therapy, and discusses interpretation of clinical trial results. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39756]

As part of the 2024 Prostate Cancer Patient Conference, Dr. Eric Small reviews Androgen Deprivation Therapy, including choices of agents, side effects, considerations in timing, duration, intensity of therapy, and discusses interpretation of clinical trial results. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39756]

As part of the 2024 Prostate Cancer Patient Conference, Dr. Eric Small reviews Androgen Deprivation Therapy, including choices of agents, side effects, considerations in timing, duration, intensity of therapy, and discusses interpretation of clinical trial results. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39756]

As part of the 2024 Prostate Cancer Patient Conference, Dr. Eric Small reviews Androgen Deprivation Therapy, including choices of agents, side effects, considerations in timing, duration, intensity of therapy, and discusses interpretation of clinical trial results. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39756]

As part of the 2024 Prostate Cancer Patient Conference, Dr. Eric Small reviews Androgen Deprivation Therapy, including choices of agents, side effects, considerations in timing, duration, intensity of therapy, and discusses interpretation of clinical trial results. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39756]

In this episode, Colin C. Pritchard, MD, PhD, a pathologist, and Heather H. Cheng, MD, PhD, a medical oncologist, discuss optimal biomarker testing to guide treatment decisions in advanced prostate cancer, with topics including: Rationale for targeting PARP in prostate cancer with ARI combinationsStudy design nuances and findings from key randomized phase III clinical trials evaluating combination therapy with a PARP inhibitor and ARI, including PROpel, MAGNITUDE, and TALAPRO-2FDA approvals of combination therapy with a PARP inhibitor and ARI, including a comparison of populations based on mutations Optimal biomarker testing for gene mutations in homologous recombination and mismatch repair pathwaysTips for optimal coordination between pathology and medical oncologyPresenters: Heather H. Cheng, MD, PhDAssociate ProfessorDepartment of MedicineDivision of Hematology and OncologyAttending PhysicianDepartment of Genitourinary Medical OncologyFred Hutchinson Cancer CenterSeattle, WashingtonColin C. Pritchard, MD, PhDCo-DirectorGenetics and Solid Tumors LaboratoryUniversity of Washington Medical CenterProfessorDepartment of Laboratory Medicine and PathologyUniversity of WashingtonSeattle, WashingtonContent based on an online CME program supported by an independent educational grant from Pfizer, Inc.Link to full program: https://bit.ly/3PFagxb

Drs. Neeraj Agarwal and Todd Morgan discuss CONTACT-02, KEYNOTE-564, CheckMate-67T, and other notable studies featured at the 2024 ASCO Genitourinary Cancers Symposium, as well as additional key abstracts in prostate, kidney, and bladder cancers that will significantly influence clinical practice. 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 and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-changing abstracts and other key advances in GU oncology featured at the 2024 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Todd Morgan, the chair of this year's ASCO GU. Dr. Morgan is a urologic surgeon, chief of urologic oncology at Michigan Medicine, and a professor of urology at the University of Michigan. Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found at asco.org/DNpod. Todd, thank you for joining us today. Dr. Todd Morgan: Thanks so much, Neeraj. It's an honor to be here and I'm just thrilled to be able to do this with you. Dr. Neeraj Agarwal: Thank you. So, the GU meeting showcased significant advancements across the spectrum of GU malignancies. Can you tell us about the hot topics that captured the headlines this year? What did you find exciting this year at the ASCO GU Symposium? Dr. Todd Morgan: The theme of this year's meeting was "20 Years of Advancing Science and Transforming Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the last 2 decades. We were thrilled to welcome over 5,200 attendees from over 70 countries, and, believe it or not, there were more than 875 abstract submissions, compared to more than 300 in the meeting's first year. Most of the participants were present in person and that was fantastic. It enabled great networking opportunities and opportunities for experts, trainees, and mentees to exchange knowledge and ideas. Without a doubt, ASCO GU remains the annual meeting in our field, and it's amazing to hear the breadth and depth of the state-of-the-art science that's presented at this meeting, and so much of it impacts patient care the second that you return home. Additionally, the meeting's focus on diversity and interactivity, networking, multidisciplinary collaboration, and evidence-based care were absolutely phenomenal from my standpoint. We had a lunch session for women's networking that was a huge success—the first time we've done that. The keynote lecture by Dr. Cheryl Lee that talked about ensuring adequate representation in clinical trials was a huge hit, and we had tremendous positive feedback from that lecture. There were also multiple featured sessions on different diagnostic and therapeutic challenges in localized, recurrent, and advanced GU cancers. And, Neeraj, my personal favorite during the symposium is always the Trainee and Early-Career Networking Luncheon on the first day and then the additional networking luncheons on the 2 following days. I had great conversations with a ton of trainees and junior faculty, and I feel so fortunate for the opportunity to get to know the future superstars in our field. So I'd like to kick it back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. A great example is Abstract 17, which was the second oral presentation delivered, and really congratulations to you, Neeraj, on sharing the exciting data from the CONTACT-02 trial which we were eagerly awaiting. And I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial? Dr. Neeraj Agarwal: Yes, Todd, I agree with you. It was such an exciting conference overall, and thank you for your leadership of this conference. So let's talk about the CONTACT-02 trial. It was a phase 3 randomized trial assessing the combination of cabozantinib and atezolizumab versus a second NHT in patients with metastatic castration-resistant prostate cancer after progression on one NHT. This patient population had to have extrapelvic soft tissue metastases, which could be liver metastases, lung metastases, or lymph nodal metastases, and about up to a quarter of patients had liver metastases. And overall, this was a high-risk patient population which was randomized to, as I said, cabozantinib plus atezolizumab versus a second line NHT. And these patients had received a prior NHT, mostly in the mCRPC setting.  The co- or dual primary endpoints were overall survival and progression-free survival (PFS). And a unique thing was that PFS was assessed only by RECIST 1.1 because, as per our discussions with regulatory authorities, the trial was focused on soft tissue metastases because of questions in the past that cabozantinib can affect bone lesions in an artifactual fashion, possibly concerns. That's why the PCWG 3 criteria were not used as the primary endpoint, but, of course, indeed used as another key endpoint, so we have information on both. Anyway, coming back to the endpoint 1:1 randomization. The randomization was stratified by presence or absence of liver metastases, prior docetaxel chemotherapy, and the setting in which NHT was given (mCSPC or CRPC). The PFS or primary endpoint was significantly improved with a 35% reduction in risk of progression or death with the cabozantinib-atezolizumab combination versus second NHT. And there was a trend for overall survival, with a hazard ratio of 0.79 favoring the cabozantinib-atezolizumab combination. Interestingly, all subgroups benefitted, regardless of age, region, site of metastases, but we decided to choose three clinical subgroups of interest such as patients with liver metastases, patients with prior docetaxel chemotherapy in the castration-sensitive setting, and bone metastases, and all these subgroups seemed to be benefitting with the strongest signal in the liver metastasis subgroup, with a 57% reduction in risk of progression or death, which I would argue we have never seen with any combination or any regimen in the metastatic prostate cancer setting yet, barring some targeted therapies in very selected patients. But overall, across the non-biomarker-selected patients, we have never seen this kind of signal. Toxicity — no discussion is complete without discussing toxicity, so I would like to highlight that. Safety signal — there were no new safety signals. The most common grade 3-4 adverse events were hypertension in 7%, anemia in 6%, which were similar in both arms, and, of course, diarrhea and fatigue in 4% each. And if we look at the secondary endpoints, such as time to chemotherapy and time to symptomatic skeletal events, they tended to favor the cabozantinib-atezolizumab. To sum it up, cabozantinib-atezolizumab showed a significant PFS benefit, with a 35% reduction in risk of progression or death, with a trend for overall survival in this patient population with an unmet need. So thank you so much, Todd, for allowing me to summarize the results of this trial. Dr. Todd Morgan: Yeah, wow. That's so impressive, and not surprising that you could so fluidly go right through all that data. Amazing. We heard some discussion of the NHT control arm in this trial. Could you discuss that for a bit? Because it obviously has implications on the similar control arm of other ongoing trials in this setting. Dr. Neeraj Agarwal: Absolutely. Pretty much all trials, every trial which has recently been reported or started in metastatic castrate-resistant prostate cancer have a similar second NHT arm. Whether there were multiple immunotherapy trials which we have just reported, or new trials which are starting or just started enrolling patients. And the reason for that is no randomized trial has ever shown superiority of docetaxel chemotherapy over a second NHT after failure of prior NHT in the mCRPC setting. That's number one. If you look at NHT as a control, it is accepted by health authorities globally with multiple recent trials which are just starting also having NHDR and it would not have been possible without the approval of global regulatory authorities across the world.  Then, if you look at the recently reported trial in the mCRPC setting with prior treatment with an NHT, there is an indication that chemotherapy may not be superior to NHT. For example, in the KEYNOTE-641 trial in patients with mCRPC with prior NHT, randomizing patients to enzalutamide plus pembrolizumab versus enzalutamide, the median PFS with enzalutamide was 9 months. This is very similar with docetaxel in patients randomized to docetaxel plus pembrolizumab versus docetaxel; the median PFS with docetaxel is 8 months or 8.3 months. And lastly, if you really want to have a comparison of chemotherapy with NHT which has been done after progression on NHT and docetaxel chemotherapy, so later line of mCRPC setting, that is the CARD trial, as you can imagine, cabazitaxel versus NHT, especially in patients with visceral metastasis, which was the point of discussion. For example, people may not feel comfortable randomizing patients to NHT compared to taxane. The hazard ratio for PFS supporting cabazitaxel was 0.79, so almost a 0.80 PFS hazard ratio, which we have never seen turning out to be a clinically significant benefit. So, if you combine all these data together, I think it was absolutely acceptable to us as investigators to have a second NHT as the control arm. And of course, when we are consenting the patient, we have to keep alternatives in mind, and we do talk about those alternatives with the patients. And if alternatives seem more applicable, we should not be talking to patients about those clinical trials or a given clinical trial in the clinic. I'm glad you brought this up, Todd, because this control NHT arm is not an issue with this trial, but all trials which should be presented in GU ASCO in the future meetings in the coming years. So, thank you. Dr. Todd Morgan: Yeah, thank you. It's such an important topic and controversy at some level, but it's a difficult problem to think about and obviously highly relevant to all the trials that we're looking at. Congrats again on that trial, that's tremendous. There was another important randomized phase 3 trial and it covers radiotherapy in patients with high-risk localized prostate cancer. Can you give us your insights on that one? Dr. Neeraj Agarwal: Yeah, Todd, I think you are referring to LBA259, titled "Long-term Results of Dose Escalation of Radiation Therapy from 70 Gy to 80 Gy Combined with Long-term Androgen Deprivation Therapy in High-risk Prostate Cancer: The GETUG-AFU 18 Randomized Trial." As you mentioned, in this randomized phase 3 trial, Dr. Christophe Hennequin and colleagues randomized patients with high-risk prostate cancer, which means they had to have either clinical stage T3 or T4 disease, or PSA ≥20 nanograms per milliliter, or a Gleason score between 8 and 10. These patients were randomized to receive ADT for 3 years combined with either dose-escalated intensity-modulated radiotherapy. So, I'd like to highlight, this was in the context of IMRT in the dose of 80 Gy or a conventional dose of 70 Gy. Now, you can argue that more people are using more than 70 Gy nowadays, but across the world, the conventional dose is still considered 70 Gy. So, 80 Gy versus 70 Gy were tested. Patients also had to have negative lymph node status on CT scans and MRI. The primary endpoint was biochemical progression-free survival or clinical progression-free survival at 5 years following the ASTRO Phoenix definition. Secondary endpoints – and these are quite important secondary endpoints – include overall survival, acute and late toxicity, and quality of life. The best part is that this trial met its primary endpoint with a 44% reduction in risk of biochemical or clinical progression or death in the dose-escalation radiotherapy arm compared with the conventional radiotherapy arm. Interestingly, a significant 52% improvement in prostate cancer-specific survival and a 39% improvement in overall survival was observed in the dose-escalated arm. So, 80 Gy continued to be superior to 70 Gy IMRT across the primary and secondary endpoints. Now, the best part is, regarding the toxicity profile, there was no significant difference between the 2 arms, with 78% of patients in the higher dose arm and 76% of patients in the conventional arm experiencing grade 2 or more toxicities. Dr. Todd Morgan: Great summary and really important, great news for our patients. Of course, it's a slightly different setting as it's high-risk localized prostate cancer. I checked in with our radiation oncologists at the University of Michigan after that [presentation] because I couldn't remember exactly where we are in terms of dose on these patients. And they were like, “Yeah, we've been doing 80 to 90 Gy for several years,” so it's great having this data to support that. And I think, as you said, the field at many centers has already moved that way. And again, the key takeaway from this abstract would be that IMRT, in combination with long-term androgen deprivation therapy, is effective and safe and increases not only the biochemical or clinical PFS rate, but also the cancer-specific survival and overall survival, again, in high-risk localized prostate cancer patients. And it does not appear to increase long-term toxicity. So really important. It'd be great to switch gears and discuss kidney cancer, if that's okay, and talk about some key abstracts in that field. What do you think? Dr. Neeraj Agarwal: There were so many exciting data in all cancers, which is amazing. So, Todd, could tell us about the LBA359, which I thought was one of the most impactful abstract presentations in the ASCO GU this year. It was titled, “Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab Versus Placebo for Treatment of Clear Cell Renal Cell Carcinoma (ccRCC)."   Dr. Todd Morgan: Yeah, this was a really big moment in our field, complete with a mid-presentation round of applause that was well deserved. And so this abstract was presented by Dr. Toni Choueiri from Dana-Farber Cancer Institute, and it included patients with clear cell renal cell carcinoma at intermediate high or high risk of recurrence, meaning that they had positive nodal disease or negative nodal disease with PT 2 and grade 4, or sarcomatoid features, or stage PT 3 or 4. These patients underwent nephrectomy with or without metastasectomy less than 12 weeks before randomization and had not received prior systemic therapy for clear cell RCC. Patients were randomized to receive either pembrolizumab 200 milligrams or placebo IV every three weeks for at least 17 cycles, or until disease recurrence, intolerable toxicity, or withdrawal of consent. Disease-free survival by investigator assessment was the primary endpoint, and overall survival was a key secondary endpoint. In this abstract, Dr. Choueiri and colleagues report results of the third prespecified interim analysis with a median follow-up of around 57 months in 496 patients receiving pembrolizumab and 498 patients receiving placebo. So, just as a reminder to the audience here, the first interim analysis reported at a median follow-up of 24 months and showed a significant reduction of 32% in the risk to recurrence or death in patients in the pembrolizumab arm. Then subsequently in November of 2021, the FDA approved pembrolizumab for the adjuvant treatment of patients with RCC who are at intermediate high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. At that time, though, overall survival data were still immature. So, at the third prespecified interim analysis with a median follow-up of around 57 months, pembrolizumab showed, for the first time in an adjuvant RCC setting, improved overall survival with a 38% reduction in the risk of death. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86% with placebo. Furthermore, the OS benefit was observed across key subgroups, including patients with non-metastatic disease, patients with metastatic but no evidence of disease, patients with PDL-1 combined positive score less than or greater than or equal to one, and patients with presence or absence of sarcomatoid features. In each of these subgroups, the forest plot looks really impressive. And the DFS benefit was similar to previously reported interim analyses with a hazard ratio of 0.72. Also, no new safety signals with pembrolizumab were observed so just tremendous data. Dr. Neeraj Agarwal: Thank you, Todd, for such a great summary of these very important results. So the key message from this abstract, as you said, is that after a median follow-up of around 57 months, which is a long follow-up, adjuvant pembrolizumab demonstrates a statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with RCC at high risk of disease recurrence after surgery. And this is, by the way, the first phase 3 study to show improved overall survival with any adjuvant therapy in RCC. Basically, this means we should continue to use adjuvant pembrolizumab or at least bring it up in our discussion with our patients who are in a similar situation with high-risk RCC after surgery. So this is great news overall. Todd, there was another kidney cancer abstract, LBA360, which compared, interestingly, subcutaneous nivolumab with intravenous nivolumab in patients with metastatic renal cell carcinoma. Could you please give us your insight about this abstract?   Dr. Todd Morgan: Sure. Really interesting study. Really interesting data that were presented. So as you mentioned, CheckMate 67T was a multicenter, randomized, open-label phase three study led by Dr. Saby George and colleagues that evaluated pharmacokinetics and objective response rate non-inferiority of subcutaneous nivolumab versus IV nivolumab in patients with locally advanced or metastatic clear cell RCC. So patients with measurable disease that progressed during or after 1 to 2 prior systemic regimens and who did not receive a prior immuno-oncology treatment were randomized 1-1 to receive either subcutaneous nivolumab 1200 milligrams every 4 weeks or IV nivolumab 3 milligrams per kilogram every two weeks until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death. The coprimary pharmacokinetics endpoints for non-inferiority testing were time-average serum concentration over the first 28 days and minimum serum concentration at steady state determined by a population pharmacokinetics analysis. A key secondary endpoint was objective response rate by independent review. So in 248 patients receiving subcutaneous nivolumab and 247 patients receiving IV nivolumab, non-inferiority for the coprimary pharmacokinetics and key-powered secondary objective response rate endpoints were met. The relative risk ratio for objective response rate was 1.33. The median PFS by independent review was 7.23 months in the subcutaneous group and 5.65 months in the IV group. Treatment-related serious adverse events occurred in 6.5% of patients in each group, and study drug toxicity led to 3 deaths in the subcutaneous group and 1 death in the IV group. These results could support using subcutaneous nivolumab as a new option to improve healthcare efficiency, especially since the average injection time with subcutaneous nivolumab was less than 5 minutes. I think we all know what issues are going on in infusion beds across the country, including, I'm sure, your center and mine. Dr. Neeraj Agarwal: Yes, absolutely. I think this is great news for our patients, Todd. Thank you. This shows that we are not only improving therapeutic options and diagnostic tools, but maybe we're also on the right track towards more practical administration routes, assisting in addressing the treatment burden and improving the efficiencies of healthcare systems. We love to have this option available for our patients, especially those who are pressed for time. So, Todd, would you like to move on to bladder cancer now?  Dr. Todd Morgan: Yeah, Neeraj, that'll be fantastic. I'm sure listeners would love to hear more about LBA530. Could you tell us more about this one, Neeraj? Dr. Neeraj Agarwal: Of course. I think this abstract is titled "Enfortumab Vedotin in Combination with Pembrolizumab Versus Chemotherapy in Previously Untreated, Locally Advanced or Metastatic Urothelial Carcinoma: Subgroup Analysis Results from EV-302," which was a global phase three study and was presented by Dr. Michiel Van Der Heijden. As our audience may recall, the EV-302 trial was presented at the ESMO 2023 meeting by Dr Tom Powles and the results were very exciting where, for the first time, a combination outperformed traditional gemcitabine-cisplatin chemotherapy. In this trial, patients with previously untreated with metastatic advanced urothelial carcinoma were randomized 1-1 to receive a 3-week cycle of a combination of enfortumab vedotin, which, as we know, is an antibody-drug conjugate targeting nectin-4 expressed on the cancer cells and pembrolizumab, which is a PD-1 inhibitor, versus gemcitabine and cisplatin or carboplatin, which were, until recently, the standard of care in this setting, and continue to be so in many countries in the world. The combination of enfortumab and pembrolizumab reduced the risk of progression or death by 55% and reduced the risk of death by 53% in the overall population. So consistent decrease in the hazard ratios for PFS and OS, and consistent improvement in overall survival and PFS in that previously reported presentation in the ESMO 2023. Now, based on these results, this combination was recently approved by the FDA in December 2023 for patients with advanced or metastatic urothelial carcinoma. So now the abstract, which was presented at the ASCO GU 2024 meeting, reported the results of a prespecified subgroup analysis. Select secondary endpoints included objective responses, duration of response, and safety. In 442 patients receiving the combination of enfortumab vedotin plus pembrolizumab, and a similar number of patients receiving chemotherapy both PFS and OS were higher for the combination of EV and pembro among prespecified subgroups such as race, platinum eligibility, PDL-1 expression, metastatic site, involvement of the liver or kidney function. Interestingly, the combination of EV and pembro reduced the risk of death by 53% in patients with visceral metastasis and 54% in patients with node-only metastasis. The improvement in PFS seems to be consistent regardless of the site of metastasis. In patients with moderate to severe renal function, the risk of death was reduced by 50% in patients receiving combination therapy. This is one of the best findings of these results because we always face challenges in treating patients with suboptimal kidney function and we cannot use cisplatin. Overall, EV plus pembro continues to show superior efficacy compared to platinum-based regimens across subgroups across the subgroups across the site of metastasis regardless of kidney function and so on. Dr. Todd Morgan: Yeah, just amazing data. I love hearing you spell it out like that. So, thank you again for the opportunity for me to sit here with you and listen to you talk about these data. It's impressive that we have been able to expand our therapeutic arsenal for urothelial carcinoma with an immune-targeting regimen that can spare our patients potential side effects of chemotherapy. What would your final takeaway on this abstract be? Dr. Neeraj Agarwal: I agree with you, Todd. I would add that the OS benefit was consistently observed across these select prespecified subgroups, including those historically associated with poor prognosis. The results of this new analysis support the finding of primary results, which indicate that EV plus pembro is a potentially new standard of care for patients with newly diagnosed, locally advanced, or metastatic urothelial carcinoma. Before we wrap up the bladder cancer session and the podcast, Todd, could you please give us insights about LBA531? Dr. Todd Morgan: Yeah, absolutely. I loved getting to hear this abstract presented. This one is titled “Ambassador,” known as the AMBASSADOR trial aligns A031501, a phase 3 randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma versus observation, that was presented by Dr. Andrea Apolo. It's an open-label, randomized, phase 3 trial that included patients with muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra. Eligible patients had pathologic tumor stage T2 or greater and/or positive pathologic nodal disease or positive margins at surgery following neoadjuvant chemotherapy, or patients with pathologic tumor stage T3 or greater and/or positive pathologic nodal disease or positive margins at surgery without prior neoadjuvant chemotherapy, and who were cisplatin ineligible or declined adjuvant cisplatin-based therapy. These patients were randomized one to one to either receive pembrolizumab 200 milligrams every 3 weeks for 1 year or observation. The dual primary endpoints were disease-free survival and overall survival. Secondary objectives included evaluation of DFS and OS in PDL-1 positive and negative patients and assessing safety. A total of 354 patients were enrolled to receive pembrolizumab and 348 to the observation arm, and 21% of the patients in the observation arm received a subsequent immune checkpoint inhibitor. At a median follow-up of 22.3 months for DFS, the median disease-free survival in the pembrolizumab arm was 29 months, while it was only 14 months in the observation arm with a hazard ratio of 0.69. At the interim analysis, OS data showed only a trend toward better outcomes in the pembrolizumab arm, which did not, however, reach statistical significance, with a median of 50.9 months in the pembrolizumab arm and 55.8 months in the observation arm with a hazard ratio of 0.98. These results could nevertheless have been impacted by the subsequent treatment of patients in the observation arm with an immune checkpoint inhibitor, especially after the FDA approval of nivolumab in 2021 for patients with muscle-invasive urothelial carcinoma, based on results of the CheckMate 274 trial. In terms of the safety profile, grade three or more adverse events occurred in 48.4% of patients in the pembrolizumab arm and 31.8% of patients in the observation arm. Dr. Neeraj Agarwal: That's great, Todd. This is such a great summary of this trial, and this is exciting news for our patients with muscle-invasive urothelial carcinoma. I'm hoping that pembrolizumab will be another option for our patients when we are discussing adjuvant immunotherapy in the clinic, moving forward very soon. With that, we have covered several abstracts addressing prostate, bladder, and kidney cancer, significantly influencing our medical practices, at least at the current moment or in the near future. Todd, thank you for sharing your insights today. These are undoubtedly exciting updates for all members of the GU oncology community, and we are grateful for your valuable contribution to the discussion. Many thanks. Dr. Todd Morgan: Thanks, for having me, Neeraj; this was really fun. I'm just really proud and excited to still be part of this field, to be part of the GU oncology field, and it continues to be exciting for all the folks who are coming up. Dr. Neeraj Agarwal: Indeed. 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. 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. 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. Todd Morgan @wandering_gu   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. Todd Morgan: Consulting or Advisory Role: Myriad Genetics, MDxHealth, TerumoBCT Research Funding (Institution): Prostate Cancer Foundation, National Institutes of Health, Department of Defence, GenomeDX Biosciences, Myriad Genetics, MDxHealth  

In this insightful episode of our podcast, Dr. Geo sits down with the distinguished Dr. Alicia Morgan, a genital urinary medical oncologist at Dana-Farber Cancer Institute and the medical director of their survivorship program. This conversation is particularly close to the heart of many of our listeners who have shared their concerns about prostate cancer treatment, especially regarding androgen deprivation therapy (ADT).Dr. Morgan, known for her patient-centered approach, brings her wealth of experience in clinical trials and patient-reported outcomes. She discusses the importance of integrating patient preferences and beliefs into clinical decision-making, a philosophy that aligns perfectly with Dr. Geo's integrative approach.Key topics include:- ADT Explained: Delving into the suitable candidates for ADT and the viability of intermittent therapy.- Chemotherapy Insights: Discussing the role of Dolcetaxel, as highlighted in the pivotal Charter trial, in treating advanced prostate cancer.- Patient-Centric Care: Dr. Morgan and Dr. Geo discuss balancing life-saving treatments with quality-of-life considerations.Since 2016, Dr. Morgan has also served as the president of the medical advisory board at Zero, a leading nonprofit dedicated to prostate cancer education and research. Her insights on prostate cancer research and treatment landscape are invaluable.Join us for this compelling conversation as we explore the nuances of prostate cancer treatment and the innovative ways Dr. Morgan helps patients navigate their journey toward health and well-being.___________Dr. Morgans website: https://www.dana-farber.org/find-a-doctor/alicia-morgans/ Cold cap for hair retention while on chemo - https://amzn.to/3M9ikEZ___________Thank you to our sponsors.This episode is brought to you by AG1 (Athletic Greens). AG1 contains 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, your nervous system, your immune system, your energy, recovery, focus, and, most things, aging. Enjoy AG1 (Athletic Greens).----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how to live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook, Instagram Click here to become a member of Dr. Geo's Health Community.Improve your urological health with Dr. Geo's formulated supplement lines: XY Wellness for Prostate cancer lifestyle and nutrition: Mr. Happy Nutraceutical Supplements for prostate health and male optimal living.You can also check out Dr. Geo's online dispensary for other supplement recommendations Dr. Geo's Supplement Store____________________________________DISCLAIMER: This audio is educational and does not constitute...

Drs Sandhya Srinivas and Tanya B. Dorff discuss metastatic hormone-sensitive prostate cancer, which patients are the best candidates for doublets vs triplets, and how we pick these patients. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988737). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Prostate Cancer https://emedicine.medscape.com/article/1967731-overview Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment https://pubmed.ncbi.nlm.nih.gov/37220335/ Triplet or Doublet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Updated Network Meta-Analysis Stratified by Disease Volume https://pubmed.ncbi.nlm.nih.gov/37055323/ PSMA PET in Imaging Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35155262/ Risks and Cancer Associations of Metachronous and Synchronous Multiple Primary Cancers: a 25-Year Retrospective Study https://pubmed.ncbi.nlm.nih.gov/34556087/ The Promise of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer: Going Beneath the Surface With Molecular Imaging https://pubmed.ncbi.nlm.nih.gov/35058322/ Gleason Score https://www.ncbi.nlm.nih.gov/books/NBK553178/ Luteinizing Hormone-Releasing Hormone (LHRH) Receptor Agonists Vs Antagonists: a Matter of the Receptors? https://pubmed.ncbi.nlm.nih.gov/23418666/ The Role of CYP17A1 in Prostate Cancer Development: Structure, Function, Mechanism of Action, Genetic Variations and Its Inhibition https://pubmed.ncbi.nlm.nih.gov/29372682/ Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial https://pubmed.ncbi.nlm.nih.gov/29384722/ Abiraterone for Prostate Cancer Not Previously Treated With Hormone Therapy https://pubmed.ncbi.nlm.nih.gov/28578639/ Abiraterone Plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/28578607/ Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP https://pubmed.ncbi.nlm.nih.gov/34928708/ Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35179323/ Abiraterone Plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in De Novo Metastatic Castration-Sensitive Prostate Cancer (PEACE-1): a Multicentre, Open-Label, Randomised, Phase 3 Study With a 2 × 2 Factorial Design https://pubmed.ncbi.nlm.nih.gov/35405085/

The inaugural episode of the European Urology podcast is here! Co-hosts Professor Declan Murphy (Melbourne) and Dr Joyce Baard (Amsterdam) highlight two key papers (details below) from this month's journal, including interviews with key authors and other experts. We also look at other highlights in this month's journal with Dr Nikita Bhatt. Plus an interview with new Editor-in-Chief, Professor Alberto Briganti. Even better on our YouTube channelPodcast Priority Papers1. Phase 2 Trial of Stereotactic Ablative Radiotherapy for Patients with Primary Renal Cancer https://www.europeanurology.com/article/S0302-2838(23)02625-8/fulltextFeatured author - Dr Raquib Hannah (Dallas)Discussant - Associate Professor Shankar Siva (Melbourne)Shankar's accompanying editorial https://www.europeanurology.com/article/S0302-2838(23)02700-8/fulltext2. The Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES https://www.europeanurology.com/article/S0302-2838(23)02723-9/fulltextFeatured author - Dr Andrew Armstrong (Durham)Discussant - Professor Alberto Briganti (Milan)

Drs Sandhya Srinivas and Rana R. McKay discuss bone health and survivorship, including risk factors and potential side effects with androgen deprivation therapy in patients with prostate cancer. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988732). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Metastases in Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/29661810/ Do Dietary Calcium and Vitamin D Matter in Men With Prostate Cancer? https://pubmed.ncbi.nlm.nih.gov/29765146/ Zoledronic Acid: A Review of Its Use in the Management of Bone Metastases and Hypercalcaemia of Malignancy https://pubmed.ncbi.nlm.nih.gov/12558465/ Denosumab in Osteoporosis https://pubmed.ncbi.nlm.nih.gov/24289327/ Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/23863050/ Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/28030702/ The Prevention of Fragility Fractures in Patients With Non-Metastatic Prostate Cancer: A Position Statement by the International Osteoporosis Foundation https://pubmed.ncbi.nlm.nih.gov/29088899/ Decreased Fracture Rate by Mandating Bone Protecting Agents in the EORTC 1333/PEACEIII Trial Combining Ra223 With Enzalutamide Versus Enzalutamide Alone: An Updated Safety Analysis. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.5002 Addition of Radium-223 to Abiraterone Acetate and Prednisone or Prednisolone in Patients With Castration-Resistant Prostate Cancer and Bone Metastases (ERA 223): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/30738780/

A new research paper was published in Oncotarget's Volume 14 on June 19, 2023, entitled, “Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer.” Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation. To investigate whether metformin mitigated ADT-related MS, researchers Devalingam Mahalingam, Salih Hanni, Anthony V. Serritella, Christos Fountzilas, Joel Michalek, Brian Hernandez, John Sarantopoulos, Paromitta Datta, Ofelia Romero, Sureshkumar Mulampurath Achutan Pillai, John Kuhn, Michael Pollak6, and Ian M. Thompson from the University of Texas Health Science Center, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Roswell Park Cancer Institute, Mays Cancer Center at University of Texas Health, Audie Murphy VA Hospital, McGill University, and Christus Health conducted a randomized double-blind phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically-relapsed or advanced prostate cancer (PC) due for ADT. “To test these hypotheses, we conducted a phase II randomized, placebo-controlled, prospective study of metformin vs. placebo in patients with advanced, castrate sensitive PC treated with ADT (NCT:01620593).” Fasting serum glucose, insulin, PSA, metformin, weight, and waist circumference (WC) were measured at baseline, week 12 and 28. The primary endpoint was a group of MS metrics. Secondary endpoints include PSA response, safety, serum metformin concentrations and analysis of downstream an mTOR target, phospho-S6-kinase. Thirty-six men were randomized to either metformin or placebo. Mean age was 68.4. Mean weight, WC and insulin levels increased in both arms. At week 12 and 28, no statistical differences in weight, WC or insulin were observed in either arm. No significant difference in percentage of patients with PSA

Join Dr. Geo in this episode as he engages in a fascinating conversation with Dr. Rana McKay, a renowned medical oncologist specializing in prostate, bladder, kidney, and testicular cancer. As an associate professor at UC San Diego School of Medicine, Dr. McKay delivers exceptional patient care and imparts her extensive knowledge to medical students, residents, and fellows.In this enthralling discussion, Dr. Geo and Dr. McKay explore the intricacies of Androgen Deprivation Therapy (ADT), a vital approach in the treatment of prostate cancer. Together, they shed light on the characteristics defining an ideal candidate for ADT and clarify the true nature of advanced prostate cancer.They uncover valuable insights into the average duration of ADT's effectiveness for men confronting advanced prostate cancer. The conversation also encompasses exploring the various types of ADT, including the intriguing concept of chemical castration. This approach offers significant promise by utilizing medications to lower androgen levels and impede the growth of prostate cancer cells. Furthermore, Dr. Geo and Dr. McKay delve into the fascinating realm of bipolar androgen therapy, an alternative approach that involves carefully calibrated testosterone doses. This discussion challenges conventional wisdom and expands our understanding of the potential benefits of this therapeutic strategy.Prepare to enrich your knowledge and gain a deeper understanding of the crucial role of androgen deprivation therapy in patients' lives. Join us for an insightful journey with Dr. Rana McKay and Dr. Geo as they explore the intricacies of this essential treatment approach.__________________Thank you to our sponsors.This episode is brought to you by ExoDx™ Prostate Test for prostate tissue. The ExoDx™ Prostate Test is a simple, non-DRE, urine-based, liquid biopsy test indicated for men 50 years of age and older with a prostate-specific antigen (PSA) 2-10ng/mL, or PSA in the “gray zone” who may be considering a biopsy. The ExoDx Prostate test provides a risk score that determines a patient's potential risk of clinically significant prostate cancer (Gleason Score ≥7). The test is included in the National Comprehensive Cancer Network (NCCN) guidelines and has been clinically validated at the cut-point of 15.6 with a 91% sensitivity and 92% negative predictive value, meaning there is less than a 9% chance of having aggressive prostate cancer below the validated cut-point of 15.6. Ask your urologist about the ExoDx Prostate Test.This episode is also brought to you by AG1 (Athletic Greens). AG1 contain 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, your nervous system, your immune system, your energy, recovery, focus, and aging. All the things. Enjoy AG1 (Athletic Greens).----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how you can live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook,

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

As part of the 2022 Prostate Cancer Patient Conference, Dr. Eric Small discusses androgen deprivation therapy and prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38561]

Our guest is Dr. Kristen Scarpato, a urologic oncologist at Vanderbilt University Medical Center in Nashville, TN. She is here to talk with us about Androgen Deprivation Therapy, or ADT, for prostate cancer. She covers information such as what is ADT, questions to ask your doctor and what to expect after treatment. Short on time? Use the below timestamps to jump to any topic section: 0:48 - Introduction 2:10 - Prostate cancer overview 3:30 - What is Androgren Deprivation Therapy (ADT)? 4:30 - Why is ADT important? 6:43 - When during treatment would ADT be considered? 9:32 - What patients benefit the most from ADT? 10:45 - What administers ADT? 12:10 - What can patients expect after ADT? 15:30 - Talking with your doctor 17:16 - Final thoughts Supported by an independent educational grant provided by Myovant Sciences LTD and Pfizer Inc. For more information, please visit www.UrologyHealth.org and don't forget to subscribe to our free digital magazine, UrologyHealth extra® at https://www.urologyhealth.org/healthy-living/urologyhealth-extra. **** December 1, 2022

Do you know which class of agents used for androgen deprivation therapy (ADT) appears to have the most cardiovascular risk? Credit available for this activity expires: 11/22/23 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/984317ecd=bdc_podcast_libsyn_mscpedu

Please visit answersincme.com/DNQ860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in urology discusses the gap in prostate cancer outcomes for Black men. Upon completion of this activity, participants should be better able to: Recognize clinical challenges in the management of prostate cancer in Black men; Describe the clinical impact of GnRH antagonists used for androgen deprivation therapy, in comparison to GnRH agonists, in men with advanced prostate cancer; and Outline patient-centered approaches to optimize outcomes for Black men with advanced prostate cancer who are eligible for androgen deprivation therapy.

You may have heard of hormone replacement therapy, but have you heard of androgen deprivation therapy (ADT)? In this episode, Brad and Warwick discuss what ADT is, how and why it is used (it's more common than you think).  They will also discuss its side effects, how to deal with them and where to go for support.   Mentioned in this episode:  - Healthy male  - MHDU Website or call 1300 00 MHDU (1300 00 6438) - MHDU Links 

Androgen Deprivation Therapy: Clinical Differences

Evolving Landscape of Androgen Deprivation Therapy in Advanced Prostate Cancer Podcast (2021) CME Available: auau.auanet.org/node/33472 This educational series is supported by independent educational grants from: Astellas AstraZeneca Lantheus Medical Imaging Merck Pfizer, Inc.

In this episode, Daniel W. Lin, MD; Alicia K. Morgans, MD, MPH; and David F. Penson, MD, answer audience questions from a live CCO webinar focused on current best practices and emerging strategies in androgen deprivation therapy, with questions including:How to select between GnRH agonists and antagonists for initial androgen deprivation therapy?How should androgen receptor inhibitors be incorporated into treatment paradigms for nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer?How should patients with prostate cancer and bone density issues be managed?How should nonmetastatic and metastatic prostate cancer be classified in light of novel imaging modalities, and how does this affect treatment?Presenters:Daniel W. Lin, MDProfessor and Chief of Urologic OncologyDepartment of UrologyUniversity of WashingtonSeattle, WashingtonAlicia K. Morgans, MD, MPHGenitourinary Medical OncologistDana-Farber Cancer InstituteBoston, MassachusettsDavid F. Penson, MDProfessor and ChairDepartment of UrologyVanderbilt University School of MedicineNashville, Tennessee Content based on an online CME program supported by educational grants from Astellas, Bayer HealthCare Pharmaceuticals Inc., Myovant Sciences Ltd, and Pfizer, Inc.  Link to full program:https://bit.ly/3iFCis5    

To obtain credit – Click Here For more information – Click Here

Featuring perspectives from Prof Simon Chowdhury and Drs Tanya B Dorff and Matthew R Smith, including the following topics: Introduction (0:00) Choice of Androgen Deprivation Therapy (2:31) Nonmetastatic Castration-Resistant Prostate Cancer (13:01 Metastatic Hormone-Sensitive Prostate Cancer (41:11) CME information and select publications

In this episode, Karim Fizazi, MD, PhD, and Alicia K. Morgans, MD, MPH, discuss the clinical implications of the latest data on androgen receptor–targeting agents in the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC). Topics include:Updated safety and patient preference data from the ARAMIS and ODENZA trialsChoice of apalutamide, darolutamide, and enzalutamideCounseling patients on adverse eventsManaging patients with asymptomatic nonmetastatic CRPCPresenters:Karim Fizazi, MD, PhDFull ProfessorCancer MedicineGustave RoussyVillejuif, France  Alicia K. Morgans, MD, MPHAssociate ProfessorDivision of OncologyDepartment of MedicineNorthwestern UniversityChicago, Illinois  Link to full program, including downloadable slides:https://bit.ly/36IEnNE

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Eric Small, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37263]

In this episode,  Wassim Abida, MD, PhD; Joaquin Mateo, MD, PhD; and Charles J. Ryan, MD, answer questions from an audience of healthcare professionals on topics related to prostate cancer and PARP inhibition including:  Germline and somatic mutation testingPARP inhibition in earlier stage diseasePARP inhibitors plus AR-targeted therapy after progression on AR-targeted therapyPARP inhibition in taxane-sensitive patientsPresenters:Wassim Abida, MD, PhDAssistant MemberAssistant Attending PhysicianGenitourinary Oncology ServiceDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkJoaquin Mateo, MD, PhDGroup LeaderProstate Cancer Translational ResearchVall d'Hebron Institute of OncologyAttending PhysicianMedical OncologyVall d'Hebron University HospitalBarcelona, SpainCharles J. Ryan, MDProfessor of MedicineB.J. Kennedy Chair in Clinical Medical OncologyDirector, Division of Hematology, Oncology and TransplantationDepartment of MedicineUniversity of MinnesotaOncologistDivision of Hematology, Oncology and TransplantationUniversity of Minnesota Health Clinics and Surgery CenterMinneapolis, MinnesotaLink to full program, including downloadable slidesets, expert commentaries, and on-demand webcast:https://bit.ly/3h1T5oR

Andrew Ruplin, PharmD, clinical instructor and oncology clinical pharmacist at Seattle Cancer Care Alliance and the University of Washington in Seattle, joins Stephanie Jardine, BSN, RN, oncology clinical specialist at ONS, to discuss new drug approvals for metastatic castration-sensitive prostate cancer. Astellas provided support for this podcast episode through an educational grant. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.75 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at myoutcomes.ons.org by May 7, 2023. The planners and faculty for this episode have no conflicts to disclose, and the episode has no commercial support. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. Episode Notes Check out these resources from today's episode: Complete this evaluation for free NCPD. Oncology Nursing Podcast Episode 149: Health Disparities and Barriers in Metastatic Castration-Sensitive Prostate Cancer ONS Voice articles: FDA approvals for abiraterone acetate, apalutamide, enzalutamide, olaparib, relugolix, and rucaparib ONS Voice article: Oncology Drug Reference Sheet: Relugolix ONS Voice article: Oncology Drug Reference Sheet: Rucaparib Oral chemotherapy education sheets for patients American Cancer Society information on prostate cancer Enzalutamide, Apalutamide, or Darolutamide: Are Apples or Bananas Best for Patients? National Cancer Institute treatment clinical trials for prostate cancer ASCENDE-RT Trial, Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy ENZAMET Trial, Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer HERO Trial, Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer Launch of ARANOTE Study Augments Development Program for Darolutamide in Prostate Cancer SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer TITAN Trial, Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer

Dr. Eric Klein of the Cleveland Clinic discusses his recent article in The Journal of Urology® titled "Androgen Deprivation Therapy in Men with Prostate Cancer Does Not Effect Risk of Infection with SARS-COV-2 ."

Commentary by Dr. Vivek Narayan

FDA 批准PARP抑制剂用于治疗前列腺癌LANCET 根治性前列腺切除术后放疗的时机Nature Biochemical Engineering 口服微生物鸡尾酒疗法用于去除肾衰竭时产生的含氮代谢物奥拉帕尼（Olaparib）奥拉帕尼（Olaparib）是一种聚ADP核糖聚合酶（PARP）抑制剂，也作用于BRCA1或BRCA2突变，之前主要用于卵巢癌、乳腺癌和胰腺癌的治疗，2020年5月被FDA批准用于治疗HRR基因突变的、去势治疗抵抗的前列腺癌。《PROfound研究：奥拉帕尼治疗转移性抗去势前列腺癌的3期临床研究》New England Journal of Medicine，2020年5月 (1)这项随机、开放标签的3期试验中，评估PARP抑制剂奥拉帕尼在去势治疗抵抗的、转移性前列腺癌患者中的疗效和安全性。队列A的245例患者存在BRCA1、BRCA2或ATM基因突变；队列B的142例患者在其他的12个预先确定的基因中存在突变。患者被随机分配至奥拉帕尼组，或对照组（接受恩扎鲁胺或阿比特龙治疗）。队列A中，奥拉帕尼组基于影像学的无进展生存期明显长于对照组（7.4个月 vs 3.6个月，P < 0.001），中位总生存期分别为18.5个月和15.1个月，在客观缓解率和疼痛程度方面奥拉帕尼组也观察到显著的益处。综合A组和B组的患者数据，奥拉帕尼组基于影像学的整体无进展生存显著优于对照组。奥拉帕尼组，贫血和恶心是主要的不良反应。结论：去势治疗抵抗的、转移性前列腺癌患者中，奥拉帕尼能显著延长无进展生存期。《PROfound研究的总体生存期分析：奥拉帕尼治疗转移性抗去势前列腺癌的生存率》New England Journal of Medicine，2020年9月 (2)PROfound研究中，奥拉帕尼组和对照组的、队列A的中位总体生存期分别为19.1个月和14.7个月（风险比 0.69，P = 0.02）；队列B的中位总生存期分别为14.1个月和11.5个月；综合队列A和队列B，中位总生存期分别为17.3个月和14.0个月。队列A中，奥拉帕尼的死亡风险比为0.42，队列B的死亡风险比为0.83，全部患者的死亡风险比为0.55。结论：去势治疗抵抗的、转移性前列腺癌患者中，奥拉帕尼显著延长总体生存时间。慢性肾脏病患者中SGLT2抑制剂的使用钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可以抑制近端小管对葡萄糖的重吸收，可以减重、改善血糖控制，但目前达格列净和卡格列净有急性肾损伤的报导，也有报导称SGLT2可能增加酮症酸中毒的风险。因此，目前FDA不推荐在eGFR

FDA 批准PARP抑制剂用于治疗前列腺癌LANCET 根治性前列腺切除术后放疗的时机Nature Biochemical Engineering 口服微生物鸡尾酒疗法用于去除肾衰竭时产生的含氮代谢物奥拉帕尼（Olaparib）奥拉帕尼（Olaparib）是一种聚ADP核糖聚合酶（PARP）抑制剂，也作用于BRCA1或BRCA2突变，之前主要用于卵巢癌、乳腺癌和胰腺癌的治疗，2020年5月被FDA批准用于治疗HRR基因突变的、去势治疗抵抗的前列腺癌。《PROfound研究：奥拉帕尼治疗转移性抗去势前列腺癌的3期临床研究》New England Journal of Medicine，2020年5月 (1)这项随机、开放标签的3期试验中，评估PARP抑制剂奥拉帕尼在去势治疗抵抗的、转移性前列腺癌患者中的疗效和安全性。队列A的245例患者存在BRCA1、BRCA2或ATM基因突变；队列B的142例患者在其他的12个预先确定的基因中存在突变。患者被随机分配至奥拉帕尼组，或对照组（接受恩扎鲁胺或阿比特龙治疗）。队列A中，奥拉帕尼组基于影像学的无进展生存期明显长于对照组（7.4个月 vs 3.6个月，P < 0.001），中位总生存期分别为18.5个月和15.1个月，在客观缓解率和疼痛程度方面奥拉帕尼组也观察到显著的益处。综合A组和B组的患者数据，奥拉帕尼组基于影像学的整体无进展生存显著优于对照组。奥拉帕尼组，贫血和恶心是主要的不良反应。结论：去势治疗抵抗的、转移性前列腺癌患者中，奥拉帕尼能显著延长无进展生存期。《PROfound研究的总体生存期分析：奥拉帕尼治疗转移性抗去势前列腺癌的生存率》New England Journal of Medicine，2020年9月 (2)PROfound研究中，奥拉帕尼组和对照组的、队列A的中位总体生存期分别为19.1个月和14.7个月（风险比 0.69，P = 0.02）；队列B的中位总生存期分别为14.1个月和11.5个月；综合队列A和队列B，中位总生存期分别为17.3个月和14.0个月。队列A中，奥拉帕尼的死亡风险比为0.42，队列B的死亡风险比为0.83，全部患者的死亡风险比为0.55。结论：去势治疗抵抗的、转移性前列腺癌患者中，奥拉帕尼显著延长总体生存时间。慢性肾脏病患者中SGLT2抑制剂的使用钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可以抑制近端小管对葡萄糖的重吸收，可以减重、改善血糖控制，但目前达格列净和卡格列净有急性肾损伤的报导，也有报导称SGLT2可能增加酮症酸中毒的风险。因此，目前FDA不推荐在eGFR

Dr Estella graduated from the University of Queensland (Medicine) in 1994 with the prize in medicine therapeutics. His endocrine training commenced in Brisbane at the Princess Alexandra Hospital and the Greenslopes hospital. He has undertaken further studies and a PhD in the area of Type 1 diabetes. Dr Estella has authored many articles and medical papers and is dedicated in keeping up to date with the latest medical developments.

This week we take a deep dive into two recently published studies, their surrounding controversy, and the broader implications. The first study was published in the journal Proceedings of the National Academy of Sciences of the USA and is titled "Physician–patient racial concordance and disparities in birthing mortality for newborns". The second was published in the New England Journal of Medicine and is titled "Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer", commonly known as the HERO trial. We discuss the HERO trial with Dr. Michael Burns of Northwestern as part of our new segment, Journal Club with a Fellow. Racial Concordance: doi.org/10.1073/pnas.1913405117 HERO: doi.org/10.1056/NEJMoa2004325 Back us on Patreon! www.patreon.com/plenarysession Check out our YouTube channel: www.youtube.com/channel/UCUibd0E2kdF9N9e-EmIbUew

Commentary by Dr. Saro Armenian

Transcription Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Jeanny Aragon-Ching, a medical oncologist who serves as the clinical program director of genitourinary cancers at Inova Schar Cancer Center in Fairfax, Virginia. She treats patients with genitourinary cancers. Dr. Aragon-Ching, welcome to the podcast. Dr. Jeanny Aragon-Ching: Thank you very much, Lauren, glad to be here. We're glad you're here. Today we're talking about new treatment options for patients with prostate cancer and renal cell carcinoma. There are new therapies available, but I wonder how do you decide which combination of drugs to use for a particular patient? Dr. Jeanny Aragon-Ching: Yes, Lauren, so there has been a lot of exciting challenges and changes actually in both prostate and advanced kidney cancer treatment, so let me first start off with advanced kidney cancers. There has been several recent approvals with a combination of immuno-oncology drugs-- so that's what they're called, I-O drugs-- and VEGF TKIs, which have paved the way for better treatment outcomes. But it is very crucial to pay attention to potential side effects, as we decide to choose between different treatment options. Dr. Jeanny Aragon-Ching: So for first-line metastatic kidney cancer treatment, the options have always included TKIs alone. So for instance, we've always had sunitinib and pazopanib, although cabozantinib soon joined the first-line TKI therapy, since about late December 2017. So more recently, combination I-Os using nivolumab and ipilimumab, as well as I-O plus TKI combinations, such as pembrolizumab and axitinib, or avelumab and axitinib, have been approved and are currently available commercially. Dr. Jeanny Aragon-Ching: So one way to distinguish these different regimens would be to evaluate what to call the IMDC criteria. So that stands for international Metastatic RCC Database Consortium criteria. So these are six different factors that the clinician can evaluate for each of their patients. So any time they have presence of anemia, leukocytosis, thrombocytosis, hypercalcemia, and a poor performance status, and if their time from diagnosis to systemic treatment is less than a year, they get a point for each. Dr. Jeanny Aragon-Ching: So if a patient has none of these factors, they would be considered to have favorable risk disease. And if they have one to two factors, then they are considered to have intermediate risk disease. If they have three or more of these, they're considered poor risk. And that's important because we want to be able to distinguish between these different categories of patients. Dr. Jeanny Aragon-Ching: So for instance, if we think about intermediate or a poor-risk disease patient, they benefit a lot from the combination of nivolumab and ipilimumab. And this is based on what you call the CheckMate 214 trial. And they reported the 30-month update at ASCO GU earlier this year. So the results showed 11.3% complete response rate compared to sunitinib, which only yielded 1.2% complete response rate. So if we look at the overall response rates for all the patients, 42% versus only 29% in the sunitinib arm. Dr. Jeanny Aragon-Ching: Now, on the other hand, pembrolizumab and axitinib with the KEYNOTE-426 Trial, also showed remarkable objective responses at around 59% versus only 35% for the sunitinib arm. And the complete responses was also impressive, occurring in about 5.8% in the combination arm. Dr. Jeanny Aragon-Ching: Now, if we look at the risk of death, it was 47% lower in the pembro/axitinib group compared to the sunitinib group. And the 18-month overall survival was 82% compared to 72% in the sunitinib arm. Now, there's another trial that looked at combination of avelumab and axitinib. This was called the JAVELIN Renal 101 Trial. And it also showed an impressive objective response rate of 55% in the PD-L1 positive population. And that's compared to sunitinib which only yielded like a 25% response rate. Dr. Jeanny Aragon-Ching: However, the concern was a primary endpoint for the JAVELIN Trial was a dual PFS, so that's Progression Free Survival, and overall survival endpoints. But the overall survival data is not yet mature at this time. And so preliminary results may be really inadequate to draw definitive conclusions as to which one is really the best. Dr. Jeanny Aragon-Ching: So regardless, the combination I-O and axitinib yielded a good response regardless of these IMVC risk groups. However, if we think about patients who have favorable risk, they really did not benefit as much from the combination pure I-O therapy, such as nivolumab and ipilimumab. And if we look further at the CheckMate 214 Trial that looked at Nivo/Ipi it showed that sunitinib actually had better responses than Nivo/Ipi in that population of favorable risk patients. So it was around 50% versus 39% in those who got Nivo/Ipi. Dr. Jeanny Aragon-Ching: However, for patients who have intermediate or poor-risk disease, I think it's very important to have shared decision-making between the provider and the patient so that they can both determine if the dual immunotherapy, I-O, I-O therapy, versus let's say, an I-O plus TKI would be the best treatment option. Dr. Jeanny Aragon-Ching: Now, it's very important to also note that beyond the discussion of efficacy, which is defined by what I mentioned earlier about CR aids and objective response rates, toxicity is very important to think about with regard to choice of treatments. So for instance, the I-O combination, the Nivo/Ipi in the in the CheckMate 214 Trial resulted in 35% of patients who required high dose prednisone. So for us, we defined this as using prednisone of 40 milligram doses or more. So that's certainly a high number, 35%. Dr. Jeanny Aragon-Ching: However, there seems to be less in the combination I-O plus TKI, only, let's say, 11% in the JAVELIN Trial. So I would say if a patient has strict contraindications and can't safely receive high dose steroids, these different regimens would have to be weighed carefully by the clinician. Dr. Jeanny Aragon-Ching: Now, on the other hand, there are certain toxicities that are far more frequent in the combination I-O/TKI, for instance, the grade 3 or 4 elevations in liver enzyme levels. So in the pembro/axitinib group, it was certainly higher than previously observed when each agent was used alone as monotherapy. So for instance, in the pembro/axi arm, it was 27% versus only 16% in the sunitinib arm. Dr. Jeanny Aragon-Ching: I would like to switch gears now for prostate cancer. So treatment for metastatic hormone-sensitive prostate cancer has undergone dramatic changes, also this far. So ADT has been what we've been using for men with metastatic disease. So ADT is short for Androgen Deprivation Therapy, that is until data on CHAARTED and STAMPEDE and LATITUDE showed that adding early docetaxel chemo or abiraterone, respectively, are better in improving overall survival outcomes. Dr. Jeanny Aragon-Ching: So recent FDA approvals of apalutamide, which is a novel anti-androgen drug, based on the TITAN Trial in the metastatic hormone-sensitive space, is really the newest addition. And it shows improved outcomes. So similarly, another trial that adds enzalutamide to ADT plus docetaxel was presented at ASCO during the plenary session, and this is called the ENZAMET trial, and it showed improvement in outcomes, with 80% of the men surviving in three years, compared to only 72% in those who got ADT plus other non-steroidal anti-androgens, like old generation drugs, like bicalutamide or nilutamide. Dr. Jeanny Aragon-Ching: However, in the pre-specified subgroup analysis of this trial, it was shown that the effects of enzalutamide was actually smaller among patients who are pre-specified to have planned early docetaxel or in those who have high-volume disease. In addition, we also are aware that while more drugs may mean better efficacy, it actually may also mean more toxicity. Dr. Jeanny Aragon-Ching: So, for instance, in the enzalutamide arm, where patients also received early docetaxel, there were more grade 2 neuropathy, like 9%, compared to 3% in the other arm. Fatigue was also far higher, at 20% versus only 14.5%, as well as other toxicities, like nail discoloration. Most importantly, 16% of patients in the enzalutamide arm, in addition to the chemo arm, had to stop because of an adverse event, compared to 4% in the non-steroidal arm. Dr. Jeanny Aragon-Ching: So this tells us that we have to really think about what to give patients with high-volume disease who are otherwise fit for chemotherapy. Since docetaxel appears to be still the most important optimal treatment option, I think adding enzalutamide to ADT and docetaxel may not confer additional benefits, and we would still better serve patients by offering ADT plus docetaxel alone for those who are otherwise fit for chemotherapy. Dr. Jeanny Aragon-Ching: In contrast, there is no direct evidence of benefit for early docetaxel in patients with low-volume disease and those who are already deemed to have good prognosis. As such, for patients with high-volume disease and not fit for chemotherapy, as well as patients with low-volume disease, we now have direct evidence that overall survival benefit is seen from using abiraterone, apalutamide, and enzalutamide when it is added to ADT. Dr. Jeanny Aragon-Ching: Now, another phase of prostate cancer that has undergone revolutionary change is what we call the non0metastatic CRPC, Castrate-Resistant Prostate Cancer space. So in this area, we now have three novel anti-antrogens that have been approved in the past year alone that can be added with ADT. So that includes apalutamide, enzalutamide, as well as darolutamide, all of which were approved just in the last year and a half alone. Dr. Jeanny Aragon-Ching: Now, they do have different side effect profiles, including CNS effects, patients can have more risk of falls, hypertension, fatigue, cardiovascular disorders. Therefore, the ultimate choice for an individual patient really depends on the physician detailing the risks and benefits of each approach and considering the patient's other health care issues. So if they have hypertension, diabetes, certainly assessing access to the care, as well as costs, and most importantly, patient preference. ASCO Daily News: That sounds very exciting. It sounds like you're really helping to move the field forward. So one of the goals is to improve the patient experience when they're undergoing treatment. What are some ways to reduce toxicity while maintaining efficacy? I know you touched on this a little bit earlier. I Dr. Jeanny Aragon-Ching:  really think the answer to that question is patient selection. Different regimens, we know, result in varying efficacy but also different side effects. So for kidney cancer, for instance, that combination I-O therapy with nivolumab and ipilimumab has the highest potential complete response rates in the order of 11% based on that 30-month follow up that I mentioned of the CheckMate 214 Trial compared to about 5.6% in the KEYNOTE pembro and axitinib study. Dr. Jeanny Aragon-Ching: However, there was also a higher incidence of patients requiring high dose steroids, that's 35%. On the other hand, when we look at the combination I-O and TKI with pembrolizumab and axitinib or avelumab and axitinib, they have good objective response rates but less CR rates, though I would certainly caution against cross-comparison between trials. Dr. Jeanny Aragon-Ching: Now, I think it's also important to know that toxicities that pertain to both I-O drug and TKI may not also be easily discernible when they're used together. So, for instance, in liver toxicities, whenever a patient manifests with liver enzyme elevation, the clinician has to determine is this autoimmune in nature versus just transaminitis from a VEGF toxicity so that treatment discontinuation for both would actually have to be undertaken. Dr. Jeanny Aragon-Ching: On the other hand, treatment side effects that led to discontinuation of any treatment was seen in about 25%. So that's a quarter of patients who received the combination pembro and axitinib. It was about 22% in those who got Nivo/Ipi, and only 4% of those who got avelumab and axitinib. So very different. Dr. Jeanny Aragon-Ching: So other things to consider, I think, would be the peculiar side effects that occur for each agent, such as perhaps, let's say, higher infusion reactions with avelumab is about 12%. And there's a need to premedicate patients. And the infusion frequency also for avelumab is every two weeks compared to, say, every three weeks for those who got pembro and every four weeks for those who are on maintenance phase of nivolumab. So it's very different in terms of convenience as well for patients. Dr. Jeanny Aragon-Ching: However, more importantly, patients and physicians alike look at overall survival as well, with both nivolumab and ipilimumab, as well as pembro and axitinib achieving overall survival hazard ratios of 0.71, and 0.53, let's say, for the pembro/axi trial, while the avelumab/axitinib had a hazard ratio of 0.78 that was not statistically significant. Dr. Jeanny Aragon-Ching: Now, if we look at prostate cancer, we look at similar issues. In order to minimize toxicity, patient selection, I think, is still key as well. So for the non-metastatic CRPC, where we can now add three potential anti-androgens, either apalutamide, enzalutamide, or darolutamide to ADT, we have to be very mindful of the possible additive side effects with hypertension, cardiovascular effects, fractures, seizures, or CNS effects. Dr. Jeanny Aragon-Ching: So one way of mitigating these side effects is just being attuned to the possible increased risk. And we have to engage our partners, the internists, cardiologists, in monitoring for metabolic syndrome side effects, for instance. So it's very important to be vigilant in watching out for any neurologic effects and frailty for our patients who may be at risk. ASCO Daily News: That's good to know. What about patients who have comorbidities? How does that affect prescribing certain therapies? Dr. Jeanny Aragon-Ching: Lauren, I think this is a very relevant question. There are certain prostate cancer patients, for instance, who are at high risk of developing toxicities, especially because of their cardiovascular, hypertension, diabetes, or even stroke. So if they already have pre-existing morbidity risks, like let's say, poorly controlled blood pressure, hyperlipidemia, they have very high blood sugar, we know that any ADT, as well as all these newer, even newer anti-androgens, have potential added risk. Dr. Jeanny Aragon-Ching: And there is, unfortunately, no additional guidelines that we can really follow, for the clinicians to follow. So awareness, I think, is very important so that we can mitigate these side effects, and we can partner with their primary care doctors so that we can immediately address emerging issues as they come. Dr. Jeanny Aragon-Ching: And this encompasses not just seizures, which really make up a very small number of the risks, but rather the mental impairment, memory loss, and a lot of these patients, remember, are elderly and also the patients we see. So they are at particularly higher risk. So it's important to take all of these into consideration. Dr. Jeanny Aragon-Ching: Now, for kidney cancers, as I alluded to earlier, given the possible autoimmune side effects from the use of I/O drugs, patients who have a pre-existing autoimmune disorders were typically excluded from a lot of those trials. However, it's also important to note that given the high potential risk to require steroids, especially for patients getting the combination nivolumab and ipilimumab, the I-O/I-O combination, it's really an important discussion to have with patients who may have a strong contraindication to receive high dose corticosteroids. So, for instance, those with uncontrolled diabetes or hypertension. ASCO Daily News: That's great to know. So what's in the pipeline for new FDA approvals? Dr. Jeanny Aragon-Ching: So yes, I think, I mean, the recent FDA approvals, for instance, in prostate cancer, the FDA has granted a breakthrough therapy designation to a PARP inhibitor called niraparib. So this is now indicated for patients with BRCA1 and 2 mutant metastatic CRPC. But they have to have failed prior toxin-based these chemo and AR, Androgen Receptor inhibitor. Dr. Jeanny Aragon-Ching: Now, for bladder cancer, I would say treatment beyond immunotherapy or immune checkpoint inhibitors have really left a big void because this is an area of increased unmet need. So recent accelerated approval was granted to a drug called erdafitinib for those patients who have progressed on or at least one prior chemotherapy and had certain FGFR3 gene mutations or FGFR2 or three gene fusions after an FDA approved test. Dr. Jeanny Aragon-Ching: Another drug that's very promising, not get approved, but was submitted to the FDA for a biologic license application is a drug called enfortumab. And this is for patients who have locally advanced or metastatic urothelial cancer who have previously received an immune checkpoint inhibitor and has received a palladium containing chemotherapy and has failed in the metastatic setting. So I think those are the recent FDA approvals that are really relevant for GU cancers. ASCO Daily News: That's great. So my last question, I'm just curious about are there recent political trials with practice-changing results that you've seen? Dr. Jeanny Aragon-Ching: Yeah, so I think that the two most influential trials would be in prostate cancer, and I've actually alluded to both of them earlier in our discussion. So one of them is the TITAN Trial which looked at apalutamide in the metastatic hormone-sensitive prostate cancer. So recall that apalutamide was initially approved actually by the FDA in February of 2018 initially for treatment of non-metastatic castrate-resistant prostate cancer. Dr. Jeanny Aragon-Ching: But more recently, in September 2019, apalutamide was approved for the hormone-sensitive metastatic prostate cancer. So this was the TITAN Trial, which was also updated and presented at ASCO GU and published at the New England Journal of Medicine at the same time. It was combined with ADT and was found to be significantly important to extend overall survival in those patients who received it. It was a 33% reduction in the risk of death. So it also improved radiographic progression free survival compared to placebo plus ADT and resulted in a 52% lower risk of radiographic progression or death. Dr. Jeanny Aragon-Ching: Another trial that I think is relevant and is practice-changing is the ENZAMET Trial. So this trial enrolled 1,125 men with metastatic hormone-sensitive prostate cancer, and they were combined with ADT and enzalutamide. And again, compared to older generation drugs, non-steroidal drugs, like bicalutamide or nilutamide or flutamide, and those patients also were allowed to receive docetaxel. Dr. Jeanny Aragon-Ching: So this was a positive trial, as I mentioned earlier. 80% of the men treated with the enzalutamide with or without docetaxel were alive compared to 72% of the men who had received just standard non-steroidal anti-androgens. So this translated to a reduction in the rate of death by 33%. Dr. Jeanny Aragon-Ching: And again, as I alluded to earlier, the subgroup analysis showed that the men who had a high-disease burden, 71% of the enzalutamide my group versus 64% of the comparator group were alive at three years. On the other hand, of the 537 men with low-disease burden, 90% in the enza group, versus 82%, were alive at three years. Dr. Jeanny Aragon-Ching: So therefore, the interpretation of this trial is really survival is only improved more markedly with enzalutamide in men who did not receive early docetaxel. Therefore, men with high-volume disease who are fit for chemotherapy are probably the most appropriate patients to receive ADT with docetaxel because additional enzalutamide also brings about seemingly more toxicity. ASCO Daily News: Wow, that's so much exciting research going on in GU cancers. Well, it's been a pleasure speaking with you. Thanks so much for being on our podcast today. Dr. Jeanny Aragon-Ching: The pleasure was all mine. Thank you, Lauren. ASCO Daily News: And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast. [MUSIC PLAYING] If you like what you hear from the ASCO podcast, please let us know. Take our listener survey and help shape the future of the ASCO Podcast Network. Visit podcast.asco.org and click on the survey link. Once again, that's podcast.asco.org. The survey will just take a few minutes to complete and will help us get to know you better. Thank you so much for listening. 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. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr. Eric Small, Professor of Medicine; Urology; and Chief, Department of Medicine/Division of Hematology/Oncology, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Professional Medical Education] [Show ID: 34965]

Dr Gwenaëlle Gravis talks to ecancertv at ASCO GU 2015 about the results of the GETUG-AFU 15 phase III trial. Long-term follow-up results suggest that the addition of docetaxel to androgen deprivation therapy did not significantly improve overall survival in patients with hormone-naïve metastatic prostate cancer.

Prof Nabid talks to ecancertv at ASCO GU 2015 about the results of a phase III study examining the "controversial" role of short-term androgen deprivation therapy in intermediate-risk prostate cancer treated with radiotherapy.

Interview with Kevin T. Nead, MD, MPhil, author of Association Between Androgen Deprivation Therapy and Risk of Dementia

Joel Nowak discusses Androgen Deprevation Therapy, also known as Hormone Treatment for advanced prostate cancer.  http://malecare.org

Men with prostate cancer are living longer, but many survive with a greater burden of treatment. More than one-third of the nearly three million prostate cancer survivors in the United States currently receive androgen deprivation therapy (ADT). ADT improves the clinical outcomes for men with prostate cancer in certain settings, but has a variety of adverse effects that may impact their long-term health. For this podcast I'm taking much of my information from a monograph printed in 2015 by the Prostate Cancer Foundation itled “Maintaining Health during Androgen Deprivation Therapy.” You can download it at the Prostate Cancer Foundation website. (http://www.pcf.org/atf/cf/{7c77d6a2-5859-4d60-af47-132fd0f85892}/MAINTAININGHEALTHADT_MONOGRAPH.PDF) ADT delays disease progression and increases survival but has a variety of potential harms including: “hot flashes” decreased desire for sexual activity and loss of erections anemia—lowered red blood cell count fatigue obesity diabetes increased triglycerides and cholesterol levels sarcopenia--general loss of muscle mass osteoporosis The primary focus for many survivors is to live free from prostate cancer. ADT helps men lead much longer lives free from pain and suffering from the cancer. By understanding some of the risks of ADT we can empower men to lead higher-quality lives during the time they are receiving this treatment

Dr. Charles Huggins groundbreaking research on prostate cancer from the 1940s about the androgen sensitivity of prostate cancer.

This is a well-annotated study demonstrating that men treated with androgen deprivation therapy for prostate cancer have impaired cognitive performance within six months of starting therapy and that a specific genetic polymorphism may lend toward greater susceptibility to cognitive impairment.

Editor's Audio Summary by Edward H. Livingston, MD, Deputy Editor, the Journal of the American Medical Association, for the July 17, 2013 issue

Androgen deprivation therapy may not be associated with an increase in cardiovascular mortality in all men but only those with a prior cardiac event due to known coronary artery disease.

A PTJ podcast titled 'Physical Function in Men With Prostate Cancer on Androgen Deprivation Therapy'