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Episode 367: Pharmacology 101: PARP Inhibitors “We know that in cells that are proliferating very quickly, including cancer cells, single-strand DNA breaks are very common. When that happens, these breaks are often repaired by the PARP enzyme, and the cells can continue their replication process. If we block PARP, that repair cannot happen. So in blocking that, these single-strand breaks then lead to double-strand breaks, which ultimately is leading to cell apoptosis,” Danielle Roman, PharmD, BCOP, manager of clinical pharmacy services at the Allegheny Health Network Cancer Institute in Pittsburgh, PA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the PARP inhibitor drug class. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by June 13, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to the use of PARP inhibitors in cancer care. Episode Notes Complete this evaluation for free NCPD. ONS Podcast™ episodes: Pharmacology 101 series Episode 330: Stay Up to Date on Safe Handling of Hazardous Drugs Episode 232: Managing Fatigue During PARP Inhibitor Maintenance Therapy Episode 227: Biomarker Testing, PARP Inhibitors, and Oral Adherence During Ovarian Cancer Maintenance Therapy ONS Voice articles: PARP Inhibitors and Ovarian Cancer Genomics May Trick PARP Inhibitors to Treat More Cancers Oncology Drug Reference Sheet: Niraparib ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (fourth edition) Safe Handling of Hazardous Drugs (fourth edition) ONS courses: Safe Handling Basics Clinical Journal of Oncology Nursing articles: PARP Inhibition: Genomics-Informed Care for Patients With Malignancies Driven by BRCA1/BRCA2 Pathogenic Variants Talazoparib Plus Enzalutamide in Patients With HRR-Deficient mCRPC: Practical Implementation Steps for Oncology Nurses and Advanced Practice Providers Oncology Nursing Forum article: Familiarity and Perceptions of Ovarian Cancer Biomarker Testing and Targeted Therapy: A Survey of Oncology Nurses in the United States Oral Anticancer Medication Care Compass: Resources for Interprofessional Navigation ONS Biomarker Database ONS Oral Anticancer Medication Learning Library ONS Oral Anticancer Medication Toolkit Oral Chemotherapy Education Sheets To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “The big toxicities here to watch for are primarily hematologic toxicities. It is one of those targeted therapies that does affect blood cell counts. So I'd say the blood cell count that is most commonly affected here is the hemoglobin. So, anemia very frequent complication that we see, probably a little bit more with olaparib compared with other drugs, but we see it as a class side effect. And we can also see neutropenia and thrombocytopenia with these agents, probably a little bit more with niraparib versus the others, but again, you can see it across all of these drugs.” TS 8:16 “We mentioned that rare risk of MDS and AML. This isn't a particularly scary thing if you talk to patients about it. Because of the rarity that we see this, it isn't something that we need to overemphasize, but I think careful monitoring of blood counts in is stressing the importance of that and early intervention here is very important.” TS 16:55 “This is a collaborative effort. And because of the home administration here, these patients do need to be followed very closely. So we are not laying eyes on them usually with the frequency that we do when we have patients actually coming into our infusion centers for treatments—so making sure that there is a plan for regular follow-up with these patients to ensure that they're getting that lab work done, that that's being looked at closely, that we're adjusting the dose if we need to based on that lab work, that we are managing the patient's fatigue. Again, that potentially dose reductions may be needed if patients are having that extreme fatigue.” TS 19:34 “I think one of those [misconceptions] could be that they're only effective in patients that have that BRCA1/2 mutation. And again, remember here that there is some data in particular disease states that we can use them and that they work in the absence of those mutations.” TS 25:12
In this episode, we dive into the tiny but powerful molecule called NAD+ — the fuel your cells need to create energy, repair damage, and keep you feeling young and strong. As we age, NAD+ levels drop, and that can lead to low energy, slower healing, and more health problems. But here's the exciting part: science is showing that we can boost NAD+ through smart lifestyle habits and supplements — helping improve energy, brainpower, heart health, and even slow down aging. We'll break it all down in simple terms: ✅ What NAD+ does in your body ✅ Why it matters for your health and aging ✅ How to naturally boost your NAD+ levels ✅ What new research is saying about its future If you want to unlock more energy, sharper thinking, and better long-term health, this episode is for you! Tune in and learn how to help your body thrive — from the inside out.
Dr. John Sweetenham shares highlights from Day 5 of the 2025 ASCO Annual Meeting, including data from large trials in advanced malignant melanoma and mCSPC plus a new approach to first-line treatment for patients with multiple myeloma who are not transplant eligible. Transcript Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 5 of the 2025 ASCO Annual Meeting. My disclosures are available in the transcript of this episode. The selected abstracts from this final day of ASCO25 include important new data from large, randomized trials in patients with advanced malignant melanoma and patients with metastatic castration-sensitive prostate cancer, as well as a new approach to the first-line treatment of patients with multiple myeloma who are not transplant eligible. Starting with LBA9500, this study was conducted in patients with completely resected stage III or IV malignant melanoma and compared the combination of relatlimab plus nivolumab versus nivolumab alone in this population. The study, named the RELATIVITY-098 trial, was presented by Dr. Georgina Long from the University of Sydney, Australia. In her introduction to the study, Dr. Long explained that the current standard of care for adjuvant therapy of resected stage III/IV melanoma is with PD-1 monotherapy with nivolumab, but that about 50% of patients will suffer from a subsequent relapse. In the first-line setting in patients with advanced or unresectable melanoma, the combination of nivolumab with the LAG-3 inhibitor, relatlimab, has been previously shown to improve progression-free survival in the RELATIVITY-047 trial. The current study evaluated this same combination in the adjuvant setting. More than 1,000 patients from 24 countries were randomized to receive either nivolumab alone (546 patients) or the combination of nivolumab with relatlimab (547 patients). Both treatments were given for a maximum of 1 year or until progression of disease, unacceptable toxicity, withdrawal, or death. Various biomarker studies were also undertaken including LAG-3 and PD-1 expression on CD8-positive T cells. The primary endpoint of the study was relapse-free survival, and Dr. Long reported that this was the same in both arms of the study. For example, at 24 months, the relapse-free survival was 64% in the monotherapy arm compared with 62% in the combination arm. The hazard ratio was 1.01 and the P value was 0.928. Metastasis-free survival was also identical in both arms. No benefit was observed for the combination in any of the prespecified subgroups. No new toxicity signals emerged compared with the RELATIVITY-047 trial. Interestingly, the baseline surface expression of LAG-3 and co-expression of LAG-3 and PD-1 on CD8 T cells in the 098 adjuvant trial were lower than in the 047 advanced disease trial, perhaps explaining why the combination did not confer benefit over nivo alone in the adjuvant setting. This is an important result, demonstrating that results from one clinical setting cannot always be extrapolated to another. Although the combination has gained some use in the adjuvant setting, this study clearly demonstrates that more drug in this situation is no better and that monotherapy remains the current standard of care. Results from the AMPLITUDE trial for patients with metastatic castration-sensitive prostate cancer with alterations in homologous recombination repair (HRR) genes, in LBA5006, were presented today by Dr. Gerhardt Attard from University College London, UK. This international, multicenter study evaluated the combination of the selective PARP inhibitor, niraparib, in combination with abiraterone acetate and prednisone. The same combination has been previously shown to improve outcomes in castration-resistant metastatic prostate cancer harboring BRCA mutations in the MAGNITUDE study. The current trial included patients with castration-sensitive disease with HRR mutations including BRCA1/2. Six hundred and ninety-six patients were randomized between niraparib, abiraterone, and prednisone plus androgen deprivation therapy, or the same combination with placebo instead of niraparib. Permitted prior therapies included no more than 6 months of prior androgen deprivation therapy and the use of docetaxel, or prior palliative radiation therapy. The primary endpoint of the study was radiographic relapse-free survival. Dr. Attard reported that the risk for radiographic progression-free survival in the whole population was significantly reduced by 37% with niraparib and abiraterone acetate plus prednisone compared with the placebo arm. The radiographic progression-free survival risk reduction with niraparib in the prespecified BRCA1/2 subgroup was 48% and reached statistical significance compared with the placebo arm. The secondary endpoint of time to symptomatic progression was also improved with niraparib in the HRR population and the BRCA1/2 subgroup. There was a trend for overall survival favoring the niraparib combination. However, the overall survival data were immature at this first interim analysis and did not yet reach statistical significance. No new safety concerns emerged with the toxicity data consistent with the MAGNITUDE study. Less than 5% more of the patients on the experimental arm discontinued treatment in comparison to the control arm. The authors conclude that the AMPLITUDE study results support the use of niraparib, abiraterone, and prednisone as a new treatment option for patients with metastatic castration- sensitive prostate cancer and BRCA and homologous recombination repair gene alterations. The results certainly support this conclusion and are potentially practice-changing. Turning to hematologic malignancies, my final selection from today's presentations is Abstract 7504, presented by Dr. Hang Quach from St Vincent's Hospital, Melbourne, Australia, and describes a novel combination of elranatamab, daratumumab, and lenalidomide in patients with newly diagnosed multiple myeloma who are not transplant-eligible – the so-called MagnetisMM-6 trial part 1. Elranatamab is a novel bispecific T-cell engaging antibody directed against BCMA and CD3, which has previously been approved for certain patients with relapsed and refractory multiple myeloma. In the present study, this was combined with lenalidomide and daratumumab in newly diagnosed patients. The report today describes the dose-finding phase of this study, which was part 1, specifically addressing so-called dose level ‘G', comprising elranatamab 76mg subcutaneously every 4 weeks plus daratumumab 1800mg subcutaneously and lenalidomide 25mg given orally. Thirty-seven patients were entered at this dose level, of whom 32 were on treatment at the time of analysis. Early response data show an overall response rate of 97.3%. With median follow up of 7.9 months, the current CR rate is 27% with a VGPR rate of almost 68%. The most frequent toxicities were hematologic, with neutropenia observed in 75%. Some cytokine release syndrome was observed in about 60% of patients, but none was greater than grade 2. The authors conclude that this combination is active in untreated multiple myeloma, with manageable toxicity and evidence of responses which appear to deepen over time. The dose-finding component of this trial is continuing and will subsequently progress into a phase 3 trial based on the data from the current study. This will compare daratumumab plus lenalidomide with the same combination plus elranatamab in previously untreated patients. That concludes our special coverage from the 2025 ASCO Annual Meeting. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts. 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 speaker: Dr. John Sweetenham Follow ASCO on social media: @ASCO on Twitter @ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. John Sweetenham: No relationships to disclose
Dr. John Sweetenham shares highlights from Day 4 of the 2025 ASCO Annual Meeting, including new research on maintenance therapy in small cell lung cancer and a virtual reality psychosocial intervention for patients undergoing hematopoietic stem cell transplantation. Transcript Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 4 of the 2025 ASCO Annual Meeting. My disclosures are available in the transcript of this episode. Today's selection features reports of 3 randomized trials in very different clinical settings: maintenance therapy in extensive small cell lung cancer (SCLC), upfront surgery in advanced ovarian cancer, and a supportive care intervention for patients undergoing hematopoietic stem cell transplantation. The first of these studies, Abstract 8006, was presented by Dr. Luis Paz-Ares from the University Hospital [October 12] in Madrid, Spain, and reports the primary results of the IMforte trial. This was a phase 3 trial evaluating the combination of lurbinectedin and atezolizumab as first-line maintenance therapy in patients with extensive small cell lung cancer. Despite some improvements in the first-line treatment of extensive small cell lung cancer with the use of checkpoint inhibitors in combination with platinum-based chemotherapy, most of the patients experience early disease progression and long-term survival remains very limited. This provides a rationale for considering a maintenance intervention. Lurbinectedin is an alkylating agent and transcription inhibitor [that is] already approved in the United States for patients with relapsed/refractory metastatic SCLC following platinum-based chemotherapy. It has been shown to synergize with immune checkpoint inhibitors in pre-clinical studies and has also been evaluated in early-phase clinical trials. The IMforte trial is a global, randomized trial in which patients are initially treated with atezolizumab, and those patients who do not progress on induction therapy are then randomized to maintenance therapy with atezolizumab alone or atezolizumab with lurbinectedin. The primary endpoints of the study were progression-free and overall survival. Four hundred and eighty-three patients were randomized and at a median follow-up of 15 months, the median progression-free survival for patients who received the combination was 5.4 months and the median overall survival was 13.2 months. This compares with 2.1 and 10.6 months, respectively, in patients who received atezolizumab only. The lurbinectedin and atezolizumab combination was generally well-tolerated, with no new or unexpected safety signals. The benefit was consistent in magnitude across all the relevant patient subgroups. This is the first phase 3 study to show a progression-free and overall survivial improvement with first-line maintenance in extensive stage SCLC and the result is likely to be practice-changing, establishing a new standard of care in this tough-to-treat disease. Next up is LBA5500, presented by Dr. Sven Mahner from LMU University in Munich, Germany. This describes the results of the TRUST study, a randomized trial of upfront surgical therapy in advanced ovarian cancer. As background, total macroscopic tumor resection with maximal effort cytoreductive surgery is the cornerstone of treatment in patients with advanced ovarian cancer. The optimal timing of such surgery remains controversial, whether it's more beneficial as a primary cytoreductive surgery before chemotherapy or in the form of interval cytoreductive surgery after 3 cycles of neoadjuvant chemotherapy. Previous studies have addressed this issue, but results have been confounded by issues of patient and center selection. The TRUST study is a randomized, international, multicenter phase 3 trial that compares the outcomes of the timing of surgery in surgically fit patients with seemingly resectable FIGO stage IIIB/IVB ovarian, tubal, and peritoneal carcinoma. To ensure consistent and adequate surgical quality, participating centers in the trial were required to obtain accreditation and undergo an onsite quality assurance review. This included assessment of infrastructure, surgical proficiency, complete resection rates, and surgical volume. Seven hundred and ninety-seven patients with advanced ovarian cancer were randomized to undergo surgery prior to therapy with 6 cycles of carboplatin and paclitaxel along with bevacizumab and a PARP inhibitor, or to have the surgery between the third and fourth cycle of the same systemic therapy. Of the initial 797 patients, 688 comprised the intent-to-treat population, of whom 345 received primary cytoreductive surgery and 343 received neoadjuvant chemotherapy followed by interval cytoreductive surgery. The results show that patients undergoing primary surgery had significantly improved progression-free survival compared with those who had interval cytoreductive surgery (median progression-free survival was 22.1 months versus 19.7 months). No difference in overall survival was observed between the 2 arms of the study. This is the first study to show a benefit for primary cytoreductive surgery, although the progression-free survival improvement was not reflected in an overall survival difference. A subgroup analysis for patients who underwent complete cytoreduction suggests a progression-free survival and survival benefit, although it isn't clear to me that the study was powered for this endpoint. Nevertheless, these are very difficult studies to perform, and the investigators should be congratulated for this robustly conducted clinical trial. Today's final abstract is 1504, presented by Dr. Hermioni Amonoo from Harvard Medical School. The trial evaluated BMT-VR, a virtual reality psychosocial intervention for patients undergoing bone marrow transplantation. This randomized trial included adult patients undergoing autologous and allogeneic transplantation. The BMT-VR platform included, among others, modules addressing psychoeducation, coping, acceptance, and gratitude. BMT-VR patients were provided with VR headsets and completed all modules during their hospitalization. Patient-reported outcomes were then assessed at 2, 4, 12, and 24 weeks post-BMT. Use of the VR tool was tracked during hospitalization. Control patients received usual care during their hospital stay and were then assessed at the same intervals post-BMT. Eighty evaluable patients were randomized, 39 to BMT-VR and 41 to usual care. Completion rates for the BMT-VR modules were high [at] around 70-75%. Patients who received the BMT-VR intervention experienced significantly improved anxiety, quality of life, and coping at 4 weeks post-BMT. In the longer term, sustained benefits were seen at 24 weeks for some endpoints including quality of life, with some benefits, including for depression and PTSD symptoms, improving longitudinally over the study period. These data are preliminary and will need to be confirmed in larger multicenter studies, but this trial demonstrates the feasibility of using virtual interventions in our patients and also provides intriguing preliminary data that they may be effective. Thanks for listening to today's report and I hope you will join me again tomorrow to hear more top takeaways from the final day of ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts. 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 speaker: Dr. John Sweetenham Follow ASCO on social media: @ASCO on Twitter @ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. John Sweetenham: No relationships to disclose
AUA2025: Embracing Multi-Disciplinary Care for Advanced Prostate Cancer: A Case-Based Update 2025 CME Available: https://auau.auanet.org/node/42997 At the conclusion of this activity, participants will be able to: 1. Initial Management of Metastatic Prostate Cancer: Evaluate and treat a patient with new diagnosed M1 prostate cancer with androgen deprivation therapy (ADT) plus be skilled to offer novel oral antiandrogens. Furthermore, to recognize high-volume new M1 prostate cancer so as to be able to partner with GU medical oncologist for docetaxel chemotherapy in a multidisciplinary team. 2. Non-Metastatic Castrate Resistant Prostate Cancer (M0 CRPC): The learner will be skilled to diagnose M0 CRPC and be able to educate patients about using either enzalutamide or apalutamide or darolutamide added to traditional ADT as a way to improve their patent's overall and radiographic progression-free survival. Furthermore, the skilled learner will be able to understand the differences between these three oral agents and to educate patients about side-effects and toxicities. Finally, understand the pros and cons of PSMA PET scan imaging in further staging in this disease Non-metastatic Castrate-Resistant Prostate Cancer (M0 CRPC): Diagnose M0 CRPC and be able to educate patients about using novel oral antiandrogens added to traditional ADT as a way to improve their patent's overall and radiographic progression-free survival. Furthermore, the skilled learner will be able to understand the differences between these novel oral agents and to educate patients about side effects and toxicities. Finally, understand the pros and cons of PSMA PET scan imaging in further staging in this disease state. 3. Metastatic Castrate-Resistant Prostate Cancer (M1 CRPC): Describe and have a working knowledge of the latest phase III RCT results for new therapies in M1 CRPC and be able to educate their patients on treatment options and participate in a multidisciplinary team caring for men with this disease state of far-advanced prostate cancer. 4. Describe that advanced prostate cancer is a complex group of disease states with an ever-changing therapeutic landscape and for providers and teams to embrace the multi-disciplinary nature of care for our patients. 5. Identify the molecular and molecular genetic underpinnings of advanced prostate cancer and recognize the future will be based on a more personalized therapy landscape including PARP inhibition, immune checkpoint agents, and novel AR targeted agents emerging in 2025 and beyond.
Dr. Rohan Garje shares the updated recommendations for the ASCO guideline on systemic therapy for patients with metastatic castration-resistant prostate cancer. He discusses the systemic therapy options for patients based on prior therapy received in the castration-sensitive and non-metastatic castration-resistant settings. He emphasizes personalizing treatment choices for each individual, considering patient-specific symptoms and signs, treatment-related toxicities, potential drug interactions, cost, and access. He also reviews recommendations on response assessment. The conversation wraps up with a discussion of potential future updates to this guideline, as the guideline transitions into a “living guideline” on mCRPC. Read the full guideline update, “Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update”. Transcript This guideline, clinical tools, and resources are available at www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology. Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Rohan Garje from Miami Cancer Institute Baptist Health South Florida, lead author on, “Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update.” Thank you for being here today, Dr. Garje. Dr. Rohan Garje: Absolutely. Thank you so much for having me, Brittany. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Garje, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to start on the content of this guideline, first, could you provide us an overview of the purpose of this guideline update? Dr. Rohan Garje: Sure. So ASCO has guidelines for prostate cancer and the specific guideline which we have updated for metastatic castrate-resistant prostate cancer was originally published in 2014. It's almost a decade. It's been a long time due for an update. Over the last decade, we have seen a lot of advances in the treatment of prostate cancer, specifically with regards to genomic testing, newer imaging modalities, and also the treatment landscape. Now we have newer options based on genomic targets such as PARP inhibitors, we have radiopharmaceuticals, a newer variant of chemotherapy, and also some specific indications for immunotherapy which were not addressed previously. Because all these advances have been new, it was really important for us to make an update. In 2022, we did make a rapid update with lutetium-177, but these additional changes which we have seen made it an appropriate time frame for us to proceed with a newer guideline. Brittany Harvey: Absolutely. It's great to hear about all these advances in the field to provide new options. So I'd like to next review the key recommendations from this guideline. So let's start with the overarching principles of practice that the panel outlined. What are these key principles? Dr. Rohan Garje: As a group, all the panel members came up with some ground rules: What are necessary for all our patients who are being treated for metastatic CRPC? First, the founding aspect was a definition for what is metastatic CRPC. So we defined metastatic CRPC as castrate level of testosterone with evidence of either new or progressive metastatic disease on radiological assessments or patients who have two consecutive rising PSAs in the setting of existing metastatic disease. We also emphasized on the need for germline and somatic testing for patients with metastatic prostate cancer at an earliest available opportunity because it is critical to select appropriate treatment and also right treatment for patients at the right time. And we actually have a concurrent guideline which addresses what genes to be tested and the timing. The other principles are patients should continue to receive androgen deprivation therapy or undergo surgical castration to maintain castrate level of testosterone. Now the key aspect with these guidelines is personalizing treatment choices. As you can see the evolution of treatment options for prostate cancer, the drugs that were initially developed and approved for prostate cancer were primarily in castrate-resistant settings, but now most of these drugs are being utilized in castrate-sensitive. So, when these patients develop castration resistance, the challenges are there are no appropriate particular drug-specific guidelines they meet. So, it's very important for the clinicians to be aware of what treatments have been received so far prior to castration resistance so that they can tailor the treatment to patient specific situations. In addition, prior to choosing a therapy, it is important for the physicians to consider patient specific symptoms or signs, treatment-related toxicities, potential drug interactions, cost, and also access to the drugs. There may be multiple treatment options available for the patients, but for a patient specific scenario, there may be a drug that may be more promising than the others. So, it is important to tailor the drug choices based on patients' unique circumstances. The panel also recommends to early integrate palliative and supportive care teams for symptom management and also discuss goals of care with the patient as each patient may have unique needs and it's important for physicians to address those concerns upfront in the care. The panel also suggests patients to receive RANK ligand inhibitors such as denosumab or bisphosphonates such as zoledronic acid to maintain the bone strength to prevent skeletal-related events. Finally, I would like to also emphasize this point about the lack of randomized clinical trial data for optimal sequencing of therapies for patients with metastatic CRPC. As I previously alluded, we have taken into account all ongoing clinical trials, prior published data, and came up with a format of preferred drugs based on prior treatments and, I think, by following these several clinical principles which I just mentioned, we can optimally choose and utilize best treatments for patients with metastatic CRPC. Brittany Harvey: Absolutely. These principles that you just outlined are important for optimal patient care, and then I want to touch on one of those things. You talked importantly about the treatments received so far. So in the next set of recommendations, the role of systemic therapy was stratified by the prior therapy received in the castration-sensitive and non-metastatic castration-resistant setting. So starting with what does the panel recommend for patients who are previously treated with androgen deprivation therapy alone in these previous settings and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: There are multiple treatment options based on prior treatment received. So for patients who received only ADT for their castration-sensitive disease, the panel strongly urges to get HRR testing to check for homologous recombinant repair related changes, specifically for BRCA1 and BRCA2 mutations, because we have three studies which have really shown significant clinical benefit for patients who have BRCA1 and BRCA2 mutations with drugs such as the combination of talazoparib and enzalutamide or olaparib with abiraterone or niraparib with abiraterone. Unless we test for those mutations, we'll not be able to give these agents upfront for the patients. In the HRR testing, if patients have HRR alterations but they are in genes which are non-BRCA, the guideline panel recommends to utilize talazoparib and enzalutamide based combination therapies. Now, if they don't have HRR alterations then there are multiple treatment choices available. It could either include androgen receptor pathway inhibitors such as abiraterone with prednisone. We could also consider docetaxel chemotherapy. The alternate choices for androgen receptor pathways include enzalutamide or the newer agents such as apalutamide and docetaxel. So, as you can see there are multiple options available, but the panel definitely emphasizes to test for HRR testing because this gives patients access to more precision therapies at this point. There may be various scenarios where a unique drug may be available for a specific patient situation. For example, patients who have very limited disease burden and may have one or two metastatic lesions, after a multidisciplinary discussion, targeted local therapies such as radiation or potentially surgery could also be offered. In select patients who have very indolent disease where they are castrate-resistant based on slow rising PSA, low-volume disease or asymptomatic disease can consider sipuleucel-T. And in patients who have bone-only metastatic disease, we could also consider radium-223, which is primarily now utilized for patients who have symptomatic bone disease. Brittany Harvey: Great. I appreciate you reviewing all those options and talking about how important it is to tailor treatment to the individual patient. So then the next category of patients, what is recommended for those who have been previously treated with ADT and an androgen receptor pathway inhibitor and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: So for patients who received ADT along with an androgen receptor pathway inhibitor, which we consider would be a most common cohort because most patients now in castration-sensitive setting are receiving androgen receptor pathway inhibitor. It was different in the past where five or six years back ADT alone was the most common treatment, but fortunately, with enough awareness and education, treatment choices have improved. Patients are now receiving ADT and ARPI as the most common choice of drug. Once again, at this point the panel emphasizes to consider HRR testing in there is enough data for us to suggest that patients who have alterations in the HRR pathway definitely will benefit with the PARP inhibitor. You know the multiple options, but specifically we speak about olaparib. And then if they are HRR-negative, we prefer patients receive agents such as docetaxel or if they are intolerant to docetaxel, consider cabazitaxel chemotherapy, options such as radium-223, and if they have a specific scenario such as MSI-high or mismatch repair deficiency, pembrolizumab could also be considered. The panel also discussed about the role of a second ARPI agent. For example, if patients progressed on one androgen receptor pathway inhibitor, the second androgen receptor pathway inhibitor may not be effective and the panel suggests to utilize alternate options before considering androgen receptor pathway inhibitor. There may be specific scenarios where a second ARPI may be meaningful, specifically, if alternate choices are not feasible for the concern of side effects or toxicities or lack of access, then a potential ARPI could be considered after progression on ARPI, but the panel definitely encourages to utilize alternate options first. Brittany Harvey: Great. Thank you for outlining those options as well for those patients. So then the next category, what is recommended for patients who have been previously treated with ADT and docetaxel? Dr. Rohan Garje: For patients who received ADT and docetaxel and were never treated with androgen receptor pathway inhibitors, the panel again emphasizes on HRR testing. If they have BRCA1 and 2 mutations, the combination therapies of talazoparib with enzalutamide, olaparib with abiraterone, or niraparib with abiraterone are all good choices. If they don't have BRCA mutations but they have other HRR mutations, the panel suggests to potentially utilize talazoparib with enzalutamide. And if they do not have any HRR alterations, the options could include androgen receptor pathway inhibitors such as abiraterone or enzalutamide. I want to emphasize that these are preferred options, but not the only options. As you can see, there are multiple options available for a particular clinical situation - so the ability of the physicians to access particular combinations, the familiarity of those drugs or the patient's unique situation where they have other medications which can potentially interact with a choice of agents. So I think based on access, based on cost and patients' concurrent illness with potential drug interactions can make one particular combination of therapy better over the other options. Brittany Harvey: Absolutely. That's key to keep in mind that access, contraindications, and cost all play a role here. So then the next set of recommendations. What are the key recommendations for patients who have previously been treated with ADT, an androgen receptor pathway inhibitor, and docetaxel who now have mCRPC? Dr. Rohan Garje: Yes. In this group, the options remain, again, broad. We utilize PSMA imaging here specifically and if they are positive on PSMA imaging, lutetium-177 is a good option. If they do not have PSMA-positive disease on PSMA imaging but if they have HRR alterations, olaparib could be utilized. And if they are negative on PSA imaging, they don't have HRR alterations, then alternate options could include cabazitaxel, radium-223. And if they have MSI-high or deficiency in mismatch repair, pembrolizumab could be utilized in this setting. Brittany Harvey: Thank you for outlining those options as well. So then next the panel addressed treatment options for de novo or treatment emergent small cell neuroendocrine carcinoma of the prostate. What are those key recommendations? Dr. Rohan Garje: Yes. This is a very high unmet need group because there are limited clinical trials, especially prospective clinical trials addressing treatment options for this group. Most of our current guidelines are always an extrapolation from lung small cell cancer based guidelines, but the panel recommends to utilize cisplatin or carboplatin along with etoposide as a preferred choice for this group. Also, an alternate option of carboplatin along with cabazitaxel could be considered for this cohort. The panel also encourages participation in clinical trials. There are numerous trials ongoing now in smaller phase studies and I think it's important for patients to consider these trials as well, because this will give them access to newer agents with potential biological targets. In addition to these agents in specific scenarios or potentially case by case basis, because we don't have prospective data, so we have made it as a select case by case basis to consider adding immunotherapy along with platinum-based chemotherapy followed by maintenance immunotherapy, which is currently a standard of care in small cell lung cancer. But the data is so limited in prostate cancer, so the panel suggested that it has to be a case by case basis only. The alternate options also include lurbinectedin, topotecan, tarlatamab upon progression on platinum-based chemotherapy. Brittany Harvey: Yes. It's important to have these recommendations in these unique situations where there is really a lack of data. So then the final set of recommendations I'd like to cover, what does the panel recommend for how clinicians should assess for response while patients are on systemic therapy and what scans are recommended for this response assessment? Dr. Rohan Garje: Yes. Again, this is another strong emphasis of the panel for global assessment of the patients. Traditionally, patients and physicians per se are heavily reliant on PSA as an accurate marker for response. This is in fact true in earlier phases of prostate cancer either in castrate-sensitive setting or localized prostate cancer setting. But as patients evolve into castrate-resistant, we don't want to heavily rely on PSA alone as a marker of response. The panel suggests to incorporate clinical response, radiological response, and also include PSA as a component, but not just rely primarily on PSA. So the panel also suggests that patients should get a bone scan and a CT scan every three to six months while on treatment to assess for appropriate response or for progression. And now one key important aspect, we are all aware about the evolving role of PSMA-based imaging with several of these new agents that are currently available. We do acknowledge these scans definitely have an important role in the care for patients with metastatic prostate cancer. Currently, the utility is primarily to select patients for lutetium-based therapy and also in situations where the traditional scans such as technitium 99 bone scan or CT scan are equivocal, then a PSMA-based imaging can be helpful. Now we are also aware that there are newer studies coming up, prospective data coming up for the role of PSMA-based imaging for response assessment. We are hoping to update the guidelines if we get access to newer data, but currently we have not recommended the utility of PSMA-based imaging for response assessments. Brittany Harvey: Understood. And I appreciate you describing where there is data here and where there's a lack of data to currently recommend. And we'll look forward to future updates of this guideline. Coming back to – at the start you mentioned how much has changed since the last guideline update. So Dr. Garje, in your view, what is the importance of this update and how will it impact both clinicians and patients with metastatic castration-resistant prostate cancer? Dr. Rohan Garje: The updated guidelines are designed to have a significant impact on clinical practice and also patient outcomes by providing clinicians with a comprehensive evidence-based framework for managing patients with metastatic CRPC. And also, by using these guidelines can make informed decisions, can select therapies tailored to patients' unique genomic status, clinical situation, where they are in the course of the cancer based on what they received previously. Also utilizing these guidelines, we can potentially improve patient outcomes, improve survival, and importantly have efficient use of healthcare resources. Brittany Harvey: Absolutely. We're always looking for ways to improve patient outcomes and survival. I want to wrap us up by talking a little bit about the outstanding questions in this field. So earlier you had mentioned about prospective data to come about PSMA PET scans, but what other outstanding questions are there for patients with metastatic castration-resistant prostate cancer? And what evidence is the panel looking forward to for future updates? Dr. Rohan Garje: We do have now rapidly evolving data specifically about the utility of the radiopharmaceutical lutetium-177 prior to chemotherapy. We are hoping that with newer data we can make some changes to the guideline based on that. We are also looking at newer drugs that are coming up in the pipeline, for example, androgen receptor degraders. We are looking at data that might potentially help based on bispecific T-cell engagers and newer radiopharmaceuticals. So I think in the next few years, we will definitely update all the guidelines again. But this time we are trying to do it more proactively. We are following a newer model. We are calling it as ‘living guidelines' where we are actually utilizing week by week updates where we look at the literature and see if there is any potential practice impacting change or publication that comes up. And we are trying to incorporate those changes as soon as they are available. That way patients and practicing physicians can get the latest information available through the guidelines as well. Brittany Harvey: That's great to hear. Yes, we'll await this data that you mentioned to continuously update this guideline and continue to improve patient outcomes for the future. So Dr. Garje, I want to thank you so much for your time to update this guideline. It was certainly a large amount of recommendations, and thank you for your time today, too. Dr. Rohan Garje: Thank you so much for having me here. And it's always nice talking to you. Brittany Harvey: And finally, thank you to our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.
AUA2025: PARP-Inhibitor Combination Treatments for the Urologic Care Team CME Available: https://auau.auanet.org/node/42822 At the conclusion of this CME activity, participants will be able to: 1. Apply the mechanism of action of PARP inhibitors and the rationale for using them in patients with advanced prostate cancer. 2. Recognize the role and importance of genetic testing in patients with mCRPC and the implications of germline mutations on response to therapy. 3. Identify best practices and utilize available guidelines for patients with mCRPC to optimize treatment success and oncologic outcomes. 4. Recognize when to use PARP inhibitors as monotherapy, the rationale and indications for combination therapy, and appropriate treatment sequencing. 5. Successfully counsel patients on the possible adverse events associated with PARP inhibitor therapies alone or in combination. ACKOWLEDGEMENTS Support provided by independent educational grants from: AstraZeneca Merck & Co., Inc.
BRCA revision mutations may explain some of the limited benefit seen in long-term follow-up studies with PARP inhibitors. Bibliography: 1: BRCA reversion mutations predict resistance. https://doi.org/10.1158/2159-8290.CD-18-0715 2: SOLO3 Final OS Data. https://doi.org/10.1200/JCO.24.00933 3: Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. https://doi.org/10.1016/j.ccell.2024.10.015
PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
PeerView Family Medicine & General Practice CME/CNE/CPE Audio Podcast
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UYH865. CME/MOC/NCPD/AAPA/IPCE credit will be available until April 14, 2026.A New Era in Treating Advanced Ovarian Cancer: Practical Tips for Maximizing the Use of PARP Inhibitors, Immunotherapy, and ADCs In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Foundation for Women's Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, and Sutro Biopharma, Inc.Disclosure information is available at the beginning of the video presentation.
Featuring an interview with Dr William K Oh, including the following topics: Use of secondary hormonal agents for patients with metastatic hormone-sensitive prostate cancer (0:00) Data supporting the clinical activity of PARP inhibitors for metastatic castration-resistant prostate cancer (mCRPC) (11:10) Radiopharmaceuticals for the treatment of mCRPC (16:53) Available data on cabozantinib for mCRPC (24:38) Cabozantinib combinations for advanced renal cell carcinoma (RCC) (26:17) Subcutaneous nivolumab versus intravenous nivolumab for advanced RCC (30:00) Addition of nivolumab to tivozanib compared to tivozanib alone in advanced relapsed/refractory RCC previously treated with an immune checkpoint inhibitor (31:28) Long-term follow-up with belzutifan for relapsed/refractory advanced RCC (33:39) Major findings from the NIAGARA study of perioperative durvalumab for muscle-invasive bladder cancer (MIBC) (35:44) Data surrounding adjuvant immunotherapy for MIBC (38:07) Clinical development of TAR-200 for high-risk non-muscle-invasive bladder cancer (39:44) Updated analysis of EV-302 study of enfortumab vedotin in combination with pembrolizumab for previously untreated advanced urothelial cancer (UC) (41:06) Implementation of emerging data in the treatment landscape of UC (41:56) CME information and select publications
How can we conserve NAD+ by preventing overactivation of the enzymes PARP-1 and CD38, which guzzle NAD+?
Join us in this insightful episode of the Oncology Brothers podcast as we dive deep into the current treatment landscape of pancreatic cancer. Drs. Rohit and Rahul Gosain are joined by Dr. Emil Lou, a medical and neuro-oncologist from the University of Minnesota, to discuss the challenges and advancements in managing this complex disease. In this episode, we covered: • The importance of a multidisciplinary approach in treating early-stage pancreatic cancer. • The role of neoadjuvant and adjuvant therapies, including the latest insights on chemotherapy regimens like FOLFIRINOX, nal-IRI and gemcitabine. • The significance of germline and next-generation sequencing (NGS) testing in personalizing treatment plans. • The current state of clinical trials and emerging therapies, including PARP inhibitors for BRCA mutations and the implications of ctDNA testing. • Prognostic discussions around metastatic pancreatic cancer and the importance of managing side effects to improve patient quality of life. Key takeaways include the necessity of balancing treatment efficacy with adverse events, the critical role of genetic testing, and the need for vigilance regarding venous thromboembolism (VTE) in pancreatic cancer patients. Don't miss this comprehensive discussion that aims to shed light on the ongoing efforts to improve outcomes for patients battling pancreatic cancer. YouTube: https://youtu.be/HCKQxmOqRTI Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Subscribe to our channel for more discussions on oncology and stay updated on the latest in cancer treatment!
Join us in this insightful episode of the Oncology Brothers podcast as we dive deep into the current treatment landscape of prostate cancer with Dr. Alan Bryce, Chief Clinical Officer and GU Medical Oncologist from City of Hope. In this episode, we explore: • The treatment paradigm for early-stage prostate cancer, including the role of active surveillance and the use of abiraterone based on the STAMPEDE trial. • The importance of understanding risk factors and treatment options for low, intermediate, and high-risk patients. • The implications of PET-PSMA imaging versus conventional CT modalities in staging and treatment decisions. • The management of biochemical recurrent disease and the significance of PSA doubling time in treatment planning. • The role of PARP inhibitors in patients with HRR mutations and the nuances of selecting appropriate therapies. • Strategies for managing metastatic disease, including the use of Lutetium-177 (Pluvicto) and cabazitaxel. Dr. Bryce provides a masterclass on navigating the complexities of prostate cancer treatment, emphasizing the need to balance between over-treatment in early disease and under-treatment in metastatic cases. YouTube: https://youtu.be/Zfu-yGmH0rg Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ If you find this episode helpful, please share it with your colleagues and leave us a review! Don't forget to check out our other episodes in the GU treatment algorithm series, including discussions on renal cell carcinoma and bladder cancer.
Do you need a recap of the latest urologic oncology research presented at GU ASCO 2025? This episode of BackTable Urology features a multidisciplinary discussion among three leading voices in urology and medical oncology – Drs. Bogdana Schmidt, Shilpa Gupta, and Ben Maughan – covering the most notable results presented at this year's meeting. --- This podcast is supported by: Photocure https://www.photocure.com/ --- SYNPOSIS First, the doctors cover a wide range of topics including PARP inhibitors for prostate cancer, HER2-targeting antibody drug conjugates in bladder cancer, adjuvant chemotherapy for upper tract urothelial carcinoma, and biomarkers such as KIM-1 in kidney cancer. Highlighting the importance of multidisciplinary collaboration, the experts also critique the COSMIC-313 trial and discuss the nuances of applying new therapeutic combinations in real-world clinical practice. --- TIMESTAMPS 00:00 - Introduction 09:20 - TALAPRO-2 Trial Insights 19:29 - Bladder Cancer: Immuno-Oncology Combinations and HER2 27:42 - NIAGARA and iNDUCT Trials 33:32 - Future Directions in Upper Tract Treatment 37:38 - Biomarkers in Kidney Cancer: KIM-1 46:43 - COSMIC-313: Triplet Therapy in Renal Cell Carcinoma 52:39 - Concluding Thoughts and Future Directions --- RESOURCES Photocure: https://www.photocure.com/
Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a leading GU medical oncologist from Dana-Farber Cancer Institute. Together, they dive into the highlights from the GU ASCO 2025 conference, covering key studies and updates in the world of genitourinary oncology. Episode Highlights: • TALAPRO-2: An in-depth discussion on the role of PARP inhibitors in prostate cancer, focusing on the study's design, findings, and the importance of germline and NGS testing. • NIAGARA Update: Insights into the new standard of care for resectable muscle-invasive bladder cancer and the promising results from the perioperative approach with Durvalumab. • CheckMate-9ER Update: A look at the combination of Cabozantinib and Nivolumab in first-line metastatic RCC, including the latest findings and implications for treatment beyond the first line. • TiNivo2: Exploring the role of Tivozanib in the treatment landscape of RCC and potential sequencing strategies. Join us for this informative discussion that aims to keep community oncologists up to date with the latest advancements in cancer care. If you find this episode helpful, please share it with your colleagues and leave us a review! YouTube: https://youtu.be/OzeHhyAdF9Q Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Don't forget to subscribe for more insights and updates from the Oncology Brothers!
Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT 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-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium? Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18? Dr. Neeraj Agarwal: Yes, Peter, 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 TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients. Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment. Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang? Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract? Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. 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. 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. Peter Hoskin Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky 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. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers
In the third episode of A Deep Dive Into HRD Testing in Ovarian Cancer, a three-part podcast series sponsored by AstraZeneca, we're speaking with Dr. David O'Malley, and Bobbie R, an ovarian cancer patient. Dr. O'Malley will highlight how HRD testing empowers ovarian cancer patients to make more informed decisions with their doctors to help guide their treatment journey, and Bobbie will provide insight into her experience with HRD testing. Dr. David O'Malley is a professor in the department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James. Bobbie is a stage 3C ovarian cancer patient who lives in Rochester, New York. Bobbie is an animal rights activist, vegetarian, and exerciser who recently retired from the healthcare field, having worked as a registered nurse and owner of a healthcare staffing firm. Following her diagnosis in July of 2021, Bobbie participated in biomarker testing which indicated that she was breast cancer gene (BRCA) negative and homologous recombination deficiency (HRD) positive. After undergoing surgery and chemotherapy as first-line treatment, Bobbie's oncologist explained that she was eligible for a poly-ADP ribose polymerase (PARP) inhibitor due to her HRD status and on March 7, 2022, Bobbie started on a PARP inhibitor for maintenance treatment. As she continues treatment in 2024, Bobbie celebrates over 45 years of marriage with her husband and looks forward to traveling the United States, reading good books, and spending time with her dogs. For more information, visit https://www.azprecisionmed.com/tumor-type/ovarian-cancer/hrd-testing.html For patient resources, please visit TestForHRD.com. This podcast does not necessarily reflect the opinions of AstraZeneca and are the spokespeople's opinions and experiences.
In the third episode of A Deep Dive Into HRD Testing in Ovarian Cancer, a three-part podcast series sponsored by AstraZeneca, we’re speaking with Dr. David O’Malley, and Bobbie R, an ovarian cancer patient. Dr. O’Malley will highlight how HRD testing empowers ovarian cancer patients to make more informed decisions with their doctors to help guide their treatment journey, and Bobbie will provide insight into her experience with HRD testing. Dr. David O’Malley is a professor in the department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James. Bobbie is a stage 3C ovarian cancer patient who lives in Rochester, New York. Bobbie is an animal rights activist, vegetarian, and exerciser who recently retired from the healthcare field, having worked as a registered nurse and owner of a healthcare staffing firm. Following her diagnosis in July of 2021, Bobbie participated in biomarker testing which indicated that she was breast cancer gene (BRCA) negative and homologous recombination deficiency (HRD) positive. After undergoing surgery and chemotherapy as first-line treatment, Bobbie’s oncologist explained that she was eligible for a poly-ADP ribose polymerase (PARP) inhibitor due to her HRD status and on March 7, 2022, Bobbie started on a PARP inhibitor for maintenance treatment. As she continues treatment in 2024, Bobbie celebrates over 45 years of marriage with her husband and looks forward to traveling the United States, reading good books, and spending time with her dogs. For more information, visit https://www.azprecisionmed.com/tumor-type/ovarian-cancer/hrd-testing.html For patient resources, please visit TestForHRD.com. This podcast does not necessarily reflect the opinions of AstraZeneca and are the spokespeople's opinions and experiences.
In the third episode of A Deep Dive Into HRD Testing in Ovarian Cancer, a three-part podcast series sponsored by AstraZeneca, we’re speaking with Dr. David O’Malley, and Bobbie R, an ovarian cancer patient. Dr. O’Malley will highlight how HRD testing empowers ovarian cancer patients to make more informed decisions with their doctors to help guide their treatment journey, and Bobbie will provide insight into her experience with HRD testing. Dr. David O’Malley is a professor in the department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James. Bobbie is a stage 3C ovarian cancer patient who lives in Rochester, New York. Bobbie is an animal rights activist, vegetarian, and exerciser who recently retired from the healthcare field, having worked as a registered nurse and owner of a healthcare staffing firm. Following her diagnosis in July of 2021, Bobbie participated in biomarker testing which indicated that she was breast cancer gene (BRCA) negative and homologous recombination deficiency (HRD) positive. After undergoing surgery and chemotherapy as first-line treatment, Bobbie’s oncologist explained that she was eligible for a poly-ADP ribose polymerase (PARP) inhibitor due to her HRD status and on March 7, 2022, Bobbie started on a PARP inhibitor for maintenance treatment. As she continues treatment in 2024, Bobbie celebrates over 45 years of marriage with her husband and looks forward to traveling the United States, reading good books, and spending time with her dogs. For more information, visit https://www.azprecisionmed.com/tumor-type/ovarian-cancer/hrd-testing.html For patient resources, please visit TestForHRD.com. This podcast does not necessarily reflect the opinions of AstraZeneca and are the spokespeople's opinions and experiences.
Welcome to the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Kevin Kalinsky, a leading breast medical oncologist and director of the breast cancer program at the Winship Cancer Institute of Emory University. Join us as we dive deep into the complexities of hormone receptor-positive breast cancer treatment. We discuss the latest advancements in treatment algorithms, including the use of OncotypeDX in premenopausal versus postmenopausal women, the role of ovarian function suppression, and the implications of new approvals like Inavolisib and CDK4-6 inhibitors. Key topics covered in this episode: • The significance of recurrence scores in dictating adjuvant chemotherapy • The ongoing OFSET trial and its potential impact on treatment decisions • Insights into the use of genomic assays like MammaPrint and RS-Clin • The evolving landscape of treatment options for locally advanced and metastatic breast cancer • The latest on PARP inhibitors, T-DXd, and other novel therapies Whether you're a medical professional or someone interested in the latest in oncology, this episode is packed with valuable insights and clinical pearls. Don't forget to subscribe for more discussions on cancer treatment, FDA approvals, and conference highlights! YouTube: https://youtu.be/_icBN3J3Bc0 Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers #OncologyBrothers #HR+ #breastcancer #HormoneReceptorPositiveCancer #oncbrothers #Podcast
Could a single molecule be the difference between vibrant longevity and early decline? Dr. Andy Salzman—Harvard-trained physician, scientist, and creator of the first PARP1 inhibitor—joins Dave to reveal the real key to living longer, fighting disease, and maximizing your energy: NAD. This master molecule fuels your mitochondria, DNA repair, and cellular resilience, but here's the catch—it plummets as you age. That means more fatigue, brain fog, inflammation, and higher risks of disease. But what if you could stop the decline and even reverse it? Dr. Salzman breaks down the game-changing science behind NAD, CD38, and cellular repair—and the fastest, most effective ways to optimize your levels for peak performance, health, and longevity. Get ready to rethink everything you thought you knew about aging, pharmaceuticals vs. supplements, and the radical new approach to living better, longer. What You'll Learn: • The #1 reason your NAD is disappearing—and how to fix it • Why NAD is the missing link in energy, DNA repair, and disease prevention • The hidden enzyme (CD38) that's sabotaging your longevity • How to supercharge mitochondria, optimize blood flow, and fight aging at the source • Why the supplement industry has it wrong—and the best way to boost NAD naturally • The shocking truth about the FDA, pharmaceuticals, and the future of anti-aging medicine Resources: • Dave Asprey's New Book - Heavily Meditated: https://daveasprey.com/heavily-meditated/ • Andrew Salzman's Instagram – https://www.instagram.com/andrew_salzman/?hl=en • 2025 Biohacking Conference: https://biohackingconference.com/2025 • Danger Coffee: https://dangercoffee.com • Dave Asprey's Website: https://daveasprey.com • Dave Asprey's Linktree: https://linktr.ee/daveasprey • Upgrade Collective – Join The Human Upgrade Podcast Live: https://www.ourupgradecollective.com • Own an Upgrade Labs: https://ownanupgradelabs.com • Upgrade Labs: https://upgradelabs.com • 40 Years of Zen – Neurofeedback Training for Advanced Cognitive Enhancement: https://40yearsofzen.com Timestamps: 00:00 Trailer 01:07 Introduction and Episode Overview 02:29 Meet Dr. Andy Salzman 02:36 From Physician to Researcher 03:39 Pharmaceuticals vs. Nutritionals 04:17 The Role of NAD in Longevity 06:32 Challenges in Longevity Research 12:58 Understanding NAD and PARP 14:34 NAD's Impact on Health 23:19 Gut Health and Longevity 27:43 Innovations in NAD Supplementation 41:27 Customer Feedback and Product Effectiveness 42:41 Surprising Benefits of NAD for Sexual Health 44:47 NAD and Vascular Health 48:46 NAD's Role in Aging and Longevity 54:03 NAD and Lifestyle Choices 01:03:02 NAD and Cognitive Function 01:06:18 NAD and Exercise 01:13:42 NAD and Sleep 01:21:54 Final Thoughts on NAD and Longevity See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
Dr. Jasmine Sukumar and Dr. Dionisia Quiroga discuss advances in adjuvant therapy for patients with early breast cancer and BRCA1/2 mutations, including how to identify patients who should receive genetic testing and the significant survival benefits of olaparib that emerged from the OlympiA trial. TRANSCRIPT Dr. Jasmine Sukumar: Hello, I'm Dr. Jasmine Sukumar, your guest host of the ASCO Daily News Podcast today. I'm an assistant professor and breast medical oncologist at the University of Texas MD Anderson Cancer Center. On today's episode, we'll be exploring advances in adjuvant therapy for high-risk early breast cancer in people with BRCA1/2 germline mutations. Joining me for this discussion is Dr. Dionisa Quiroga, an assistant professor and breast medical oncologist at the Ohio State University Comprehensive Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Quiroga, it's great to have you on the podcast. Thanks for being here. Dr. Dionisia Quiroga: Thank you. Looking forward to discussing this important topic. Dr. Jasmine Sukumar: Let's start by going over who should be tested for BRCA1/2 genetic mutations. How do you identify patients with breast cancer in your clinic who should be offered BRCA1/2 genetic testing? Dr. Dionisia Quiroga: So, guidelines on who to offer testing to somewhat differ between organizations at this point. I would say, generally, I do follow our current ASCO-Society of Surgical Oncology (SSO) Guidelines, though. Those guidelines recommend that BRCA1/2 mutation testing be offered to all patients who are diagnosed with breast cancer and are 65 years old or younger. For those that are older than 65 years old, there are additional factors to really take into account to decide on who to recommend testing for. Some of this has to do with personal and family history as well as ancestry. The NCCN also has their own specific guidelines for who to offer testing to. For example, people assigned male at birth; those who are found to have a second breast primary; those who are diagnosed at a young age; and those with significant family history should also be offered BRCA1/2 testing. I think, very important for our discussion today, ASCO and SSO also made a very important point that all patients who may be eligible for PARP inhibitor therapy should be offered testing. So clearly this includes a large amount of our patient population. In my practice, we often refer to our Cancer Genetics Program. We're fortunate to have many experienced genetic counselors who can complete pre-test and post-test counseling with our patients. However, in settings where this may not be accessible to patients, it can also be appropriate for oncology providers to order the testing and ideally perform some of this counseling as well. Dr. Jasmine Sukumar: Thank you Dr. Quiroga. Let's next review where we are in current clinical practice guidelines. What current options do we have for adjuvant therapy specific to people with high-risk early breast cancer and BRCA1/2 genetic mutations? Dr. Dionisia Quiroga: Our current guidelines recommend adjuvant olaparib for one year for individuals with HER2-negative high risk breast cancer. This approval largely came from the data and the results of the OlympiA trial. This was a prospective phase 3, double blind, randomized clinical trial. It enrolled patients who had been diagnosed with HER2-negative early-stage breast cancer who also carried germline pathogenic or likely pathogenic variants of either the BRCA1 and/or BRCA2 genes. The disease also had to be considered high-risk and there were several criteria that had to be evaluated to deem whether or not these patients were high-risk. For example, those who are treated with neoadjuvant chemotherapy, if they had disease that was triple-negative, they needed to have some level of invasive residual disease at time of surgery. Alternatively, if the disease was hormone receptor-positive, they needed to have residual disease and a calculated CPS + EG score of 3 or higher. This scoring system is something that estimates relapse probability on the basis of clinical and pathologic stage, ER status, and histologic grade, and this will give you a score ranging from 0 to 6. In general, the higher the score, the worse the prognosis. This calculator though is available to the public online to allow providers to calculate this risk. For the subset of patients who received adjuvant chemotherapy, for them to qualify for the OlympiA trial, if they had triple-negative disease, they needed to have a tumor of at least 2 cm or greater and/or have positive lymph nodes for disease. For hormone receptor-positive disease that was treated with adjuvant chemotherapy, they were required to have four or more pathologically confirmed positive lymph nodes at time of surgery. From this specified pool, patients were then randomized 1:1 to get either adjuvant olaparib starting at 300 mg twice a day or a matching placebo twice a day after they had completed surgery, chemotherapy and radiation treatment if needed. Dr. Jasmine Sukumar: And what were the outcomes of this study? Dr. Dionisia Quiroga: The study ended up enrolling over 1,800 patients and from these 1,800 patients, 70% had a BRCA1 mutation while 30% had a BRCA2 mutation. About 80% of the patients had triple-negative disease compared to hormone receptor-positive disease. Interestingly, about half of all patients enrolled had received neoadjuvant chemotherapy while the other half received adjuvant chemotherapy. Looking at the outcomes, this was overall a very positive study. We actually now have outcomes data from a median of about 6 years out. This was just reported in December at the 2024 San Antonio Breast Cancer Symposium. There was found to be a 9.4% absolute difference in six-year invasive disease-free survival favoring the olaparib arm over the placebo arm. What was also interesting is that this was consistent across multiple subgroups of patients and the benefit was really seen whether or not they had hormone receptor-positive or triple-negative disease. The absolute difference in distant disease-free survival was also high at 7.8% and additionally favored olaparib. Most importantly, there was found to be a significant overall survival benefit. The six-year overall survival was 87.5% in the olaparib group compared to 83.2% in the placebo group. This translates to about a 4.4% difference and a relative 28% overall survival benefit in using olaparib. Now, future follow up is going to be very important. Follow up for this study is actually planned to continue out until June 2029 so we can continue to observe if these survival curves will continue to branch apart as they have so far at each follow up. And I think this is especially important for those patients diagnosed with hormone receptor-positive cancers because we know those patients are at particular risk for later recurrences. As an additional side note, the researchers also noted that there were fewer primary malignancies in the olaparib group, not just of the breast but also primary ovarian or fallopian tube cancers as well, which is not completely surprising knowing that this drug is also heavily used and beneficial in different types of gynecologic cancers. Ultimately, the amount of adverse events reported have been low with only about 9.9% of patients receiving olaparib needing to discontinue drug due to adverse events, and this is compared to 4.2% reported in the placebo group. Dr. Jasmine Sukumar: You mentioned that the OlympiA trial showed an overall survival benefit, but interestingly the OlympiAD trial looking at olaparib versus chemotherapy in patients with advanced metastatic HER2-negative breast cancer did not show a significant overall survival benefit. Could you discuss those differences? Dr. Dionisia Quiroga: I agree, that's a very good point. So OlympiA's comparator arm was, of course, a placebo. So while this isn't the same as comparing to chemotherapy, it does still potentially suggest that there is a degree of benefit that olaparib can provide when it's introduced in the early local disease setting compared to advanced metastatic disease. I think we need more future trials looking at potential other combinations to see if we can improve the efficacy of PARP inhibitors in the metastatic setting. Dr. Jasmine Sukumar: For patients who do choose to proceed with use of adjuvant olaparib due to the promising efficacy, what side effects should oncologists counsel their patients about? Dr. Dionisia Quiroga: The most common notable side effects, I would say with olaparib and other PARP inhibitors are really cytopenias. Gastrointestinal side effects such as nausea and vomiting can occur as well as fatigue. There are some less common but potentially more serious side effects that we should counsel our patients on. This includes pneumonitis. So counseling patients on if they're short of breath or experiencing cough to let their provider know. Venous thromboembolism can also be increased rates of occurrence. And then of course myelodysplastic syndromes or acute myeloid leukemia is something that we often are concerned about. That being said, I think it should be noted that interestingly in the OlympiA trial so far, there have been less new cases of MDS and AML in the olaparib group than actually what's been reported in the placebo group at this median follow up of over six years out. So we'll need to continue to monitor this endpoint over time, but I do think this provides some reassurance. Dr. Jasmine Sukumar: Since the initiation of the OlympiA trial, other adjuvant treatments have also been studied and FDA approved for non-metastatic HER2-negative breast cancer. So for example, the CREATE-X trial established adjuvant capecitabine as an FDA approved treatment option in patients with triple-negative breast cancer who had residual disease following neoadjuvant chemotherapy. So if a patient with triple-negative breast cancer with residual disease is eligible for both adjuvant olaparib and adjuvant capecitabine treatments, how do you decide amongst the two? Dr. Dionisia Quiroga: If a patient's eligible for both, I honestly often favor olaparib, and I do this because I find the data for adjuvant olaparib a little bit more compelling. There are also differences in toxicity profile and treatment duration between the two that I think we should discuss with patients. For example, olaparib is supposed to be taken for a year total, whereas with capecitabine we typically treat for six to eight cycles with each cycle taking three weeks. There are some who may also sequence the two drugs in very high-risk disease. However, this is very much a data free zone. We don't have any current clinical trials really comparing these two or if sequencing of these agents is appropriate. So I don't currently do this in my own clinical practice. Dr. Jasmine Sukumar: Nowadays, almost all patients with stage 2 to 3 triple-negative breast cancer will be offered neoadjuvant chemotherapy plus immune checkpoint inhibitor therapy pembrolizumab per our KEYNOTE-522 trial data. With our current approach, pembrolizumab is continued into the adjuvant setting regardless of surgical outcome, so that patients receive a year total of immunotherapy. So in patients with residual disease and a BRCA germline mutation, do you suggest using adjuvant olaparib concurrently with pembrolizumab? Do we have any data to support that approach? Dr. Dionisia Quiroga: I do. I do use them concurrently. If a patient is eligible for adjuvant olaparib, I would use it the same way as if they were not on pembrolizumab. That being said, there are no large studies currently that have shown what the benefit or the toxicity of pembrolizumab plus olaparib are for early-stage disease. However, we do have some safety data of this combinatorial approach from other studies. For example, the phase 2/3 KEYLYNK-009 study showed that patients with advanced metastatic triple-negative breast cancer who were receiving concurrent pembrolizumab and olaparib had a manageable safety profile, particularly as the toxicities of these drugs alone don't tend to overlap. Dr. Jasmine Sukumar: And what about endocrine therapy for those that also have hormone receptor-positive disease? Dr. Dionisia Quiroga: Adjuvant endocrine therapy should definitely be continued while patients are on olaparib if they're hormone receptor-positive. An important component of this will also likely be ovarian suppression, which should include recommendation of risk reducing bilateral salpingo oophorectomy due to the risk of ovarian cancer development in patients who carry BRCA1/2 gene mutations. In most cases, this should happen at age 40 or before for those that carry a BRCA1 mutation, and at age 45 or prior for those with BRCA2 mutations. Dr. Jasmine Sukumar: And do you also consider adjuvant bisphosphonates in this context? Dr. Dionisia Quiroga: Yes. Like adjuvant endocrine therapy, adjuvant bisphosphonates were also instructed to be given according to standard guidelines in the OlympiA trial, so I would recommend use of bisphosphonates when indicated. You can refer to the ASCO Ontario Health Guidelines on Adjuvant Bone-Modifying Therapy Breast Cancer to guide that decision in order to utilize this due to multiple clinical benefits. It doesn't just help in terms of adjuvant breast cancer treatment but also reduction of fracture rate and down the line, improved breast cancer mortality. Dr. Jasmine Sukumar: Particularly in hormone receptor-positive breast cancer, another adjuvant therapy option that was not available when the OlympiA trial started are the CDK4/6 inhibitors, ribociclib and abemaciclib, based on the NATALEE and monarchE studies. So how do you consider the use of these adjuvant therapy drugs in the context of olaparib and BRCA mutations? Dr. Dionisia Quiroga: Yeah, so we are definitely in a data-free zone here. And that's in part because the NATALEE and the monarchE studies are still ongoing and reporting data out at the same time that we're getting updated OlympiA data. So unlike some of our other adjuvant treatments that we discussed, where olaparib could be safely given concurrently, the risk of myelosuppression and using both a CDK4/6 inhibitor and a PARP inhibitor at the same time would be too high. In some cases, even if a patient has a BRCA1/2 mutation, they may not meet that specified inclusion criteria that OlympiA set for what they consider to be high-risk disease. And we know from the NATALEE and the monarchE trial there are also different markers that they use to denote high-risk disease. So it's possible, for example, in the NATALEE trial that looks specifically at adjuvant ribociclib, they included a much larger pool of hormone receptor-positive early-stage breast cancers, including a subset that did not have positive axillary lymph nodes. In cases where patients would qualify for both olaparib and a CDK4/6 inhibitor, I think this is worth a nuanced discussion with our patients about the potential benefits, risks and administration of these drugs. I think another point to bring up is the cost associated with these drugs and the length of time patients will be on for, because financial toxicity is always something that we should bring up with patients as well. When sequencing these in high-risk disease, my practice is to generally favor olaparib first due to the overall survival data. There is also some data to support that patients with BRCA1/2 germline mutations may not respond quite as well to CDK4/6 inhibitors compared to those without. But again, this is still outside of the purview of current guidelines. Fortunately, we have more potential choices for patients, and that's a good thing, but shared decision making also needs to be key. Dr. Jasmine Sukumar: And while our focus today is on adjuvant treatment for people who carry germline BRCA mutations, what about other related gene mutations such as PALB2 pathogenic variant? Dr. Dionisia Quiroga: That's a great question. Clinical trials in the advanced metastatic setting have shown that there is efficacy of olaparib in the setting for PALB2 mutations. This is largely based on the TBCRC 048 phase 2 trial and that provided a Category 2B NCCN recommendation for patients with these PALB2 gene mutations. However, we're really still lacking enough clinical data for use in early-stage disease, so I don't currently use adjuvant olaparib in this case. I am definitely eager for more data in this area as the efficacy of PARP inhibitors in PALB2 gene mutations is very compelling. I think also, in the same line, there's been some data for somatic BRCA1/2 mutations in the metastatic setting, but we still have a lack of data for the early stage setting here as well. Dr. Jasmine Sukumar: Thank you Dr. Quiroga, for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Dionisia Quiroga: Thank you, Dr. Sukumar. Dr. Jasmine Sukumar: And thank you to our listeners for your time today. You'll find links to the studies 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. 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. Dionisa Quiroga @quirogad @quirogad.bsky.social Dr. Jasmine Sukumar @JasmineSukumar @jasmine.sukumar.bsky.social Follow ASCO on social media: @ASCO on X @ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Dionisia Quiroga: No relationships to disclose Dr. Jasmine Sukumar: Honoraria: Sanofi (Immediate Family Member)
Dr. Stéphanie Gaillard and Dr. Bill Tew share updates to the evidence-based guideline on neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer. They highlight recommendations across ten clinical questions, addressing initial assessment, primary cytoreductive surgery, neoadjuvant chemotherapy (NACT), tests and/or procedures that should be completed before NACT, preferred chemotherapy regimens, timing of interval cytoreductive surgery (ICS), hyperthermic intraperitoneal chemotherapy (HIPEC), post ICS-chemotherapy, maintenance therapy, and options for those without a clinical response to NACT. They highlight the evidence supporting these recommendations and emphasize the importance of this guideline for clinicians and patients. Read the full guideline update, “Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update” at www.asco.org/gynecologic-cancer-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology. Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Stéphanie Gaillard from Johns Hopkins University and Dr. Bill Tew from Memorial Sloan Kettering Cancer Center, co-chairs on “Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update.” Thank you for being here today, Dr. Gaillard and Dr. Tew. Dr. Bill Tew: Thank you for having us. Dr. Stéphanie Gaillard: Yeah, thank you. It's great to be here. Brittany Harvey: Great. Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Gaillard and Dr. Tew, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the content here, first, Dr. Tew, could you describe what prompted this update to the neoadjuvant chemotherapy for ovarian cancer guideline? And what is the scope of this update? Dr. Bill Tew: Yeah. It's been almost a decade since ASCO first published its neoadjuvant chemotherapy guidelines for women with newly diagnosed ovarian cancer, and over that 10-year period, there's really been a major shift in how oncologists treat patients in the U.S. If you look at the National Cancer Database, between 2010 and 2021, the proportion of patients with advanced ovarian cancer who underwent primary surgery fell from about 70% to about 37%. And there's been a doubling in the amount of neoadjuvant chemotherapy used. So we wanted to take a look at that and really both highlight the appropriate patient populations for primary surgery versus new adjuvant chemotherapy, as well as review any studies that have been published since then. There's been, I think, about 61 trials published, nine randomized trials alone in the last 10 years. And the scope of the guideline was really not only the neoadjuvant chemotherapy and surgical questions, but also to touch upon some new treatments that have come to the forefront in newly diagnosed ovarian cancer, including heated intraperitoneal chemotherapy or HIPEC, as well as the integration of maintenance therapy, particularly bevacizumab and PARP inhibitors. Brittany Harvey: Understood. That's a large amount of new evidence to review in this Update. Then, next, Dr. Gaillard, I'd like to review the key recommendations across the 10 clinical questions that the guideline addressed. So, starting with: What is recommended regarding initial assessment for patients with newly diagnosed pelvic masses and/or upper abdominal or peritoneal disease? Dr. Stéphanie Gaillard: Sure. So in talking about the first guidelines, the first one that we addressed was how to do the initial assessment for these patients. And first, and probably most critically, it's important to recognize that these patients really should be evaluated by a gynecologic oncologist prior to initiation of any therapy, whether that means a primary cytoreductive surgery or neoadjuvant chemotherapy, because really, they are the best ones to determine the pathway that the patient should take. The initial assessment should involve a CA-125, a CT of the abdomen and pelvis with oral and IV contrast, if not contraindicated, and then also chest imaging, in which a CT is really the preferred modality. And that helps to evaluate the extent of disease and the feasibility of the surgical resection. Now, there may be some other tools that could be helpful to also refine this assessment. So, for example, a laparoscopy can really help to determine the feasibility of surgical resection as well as the extent of disease. Further imaging, such as diffusion-weighted MRI or FDG-PET scans can be helpful, as well as ultrasounds. And then also an endometrial biopsy. And that was newly added because there really has been a divergence of treatment for endometrial cancer versus ovarian cancer. And so it's really important to determine upfront where the source of the disease is coming from. Brittany Harvey: I appreciate you describing those recommendations surrounding initial assessment. So following this assessment, Dr. Tew, which patients with newly diagnosed advanced epithelial ovarian cancer should be recommended primary cytoreductive surgery? Dr. Bill Tew: The key thing here is if the GYN oncology surgeon feels that they have a high likelihood of achieving a complete cytoreduction with acceptable morbidity, the panel overwhelmingly agrees that primary cytoreduction surgery should be recommended over chemotherapy. And we know that surgery is really the cornerstone to achieving clinical remission. And our concern is that neoadjuvant chemotherapy may be overused in this fit population. Sometimes it is challenging to determine truly if a patient has a high likelihood of complete cytoreduction or what is acceptable morbidity. But an evaluation with performance status, fitness, looking at age or frailty, nutritional status, as well as a review of imaging studies to plan and determine for who is the right patient for primary surgery is key. Brittany Harvey: And then the title of this guideline, Dr. Gaillard, for which patients is neoadjuvant chemotherapy recommended? Dr. Stéphanie Gaillard: Yeah. So there's really two patient populations that we think are best suited to receive neoadjuvant chemotherapy. Those may be patients who are fit for a primary cytoreductive surgery, but they're unlikely to have a complete cytoreduction if they were to go to surgery directly. And so that's where neoadjuvant chemotherapy can be very helpful in terms of increasing the ability to obtain a complete cytoreduction. The second population is those who are newly diagnosed who have a high perioperative risk, and so they're not fit to go to surgery directly. And so it may be better to start with neoadjuvant chemotherapy and then do an interval cytoreductive surgery. Again, I just want to emphasize the importance of including a gynecologic oncologist when making these determinations for patients. Brittany Harvey: Absolutely. So then the next clinical question. Dr. Tew, for those patients with newly diagnosed stage 3 to 4 epithelial ovarian cancer, what tests and or procedures are recommended before neoadjuvant chemotherapy is delivered? Dr. Bill Tew: The key test is to confirm the proper diagnosis, and that requires histological confirmation with a core biopsy. And this was a point the panel strongly emphasized, which is a core biopsy is a much better diagnostic tool compared to cytology alone. But there will be cases, exceptional cases, where a core biopsy cannot be performed. And in those settings, cytology combined with serum CA-125 and CEA is acceptable to exclude a non-gynecologic cancer. The other reason why cord biopsy is strongly preferred is because we already need to start thinking about germline and somatic testing for BRCA1 and 2. This information is important as we start to think about maintenance strategies for our patients. And so having that information early can help tailor the first-line chemotherapy regimen. Brittany Harvey: So then you've described who should be receiving neoadjuvant chemotherapy, but Dr. Gaillard, for those who are receiving neoadjuvant chemo, what is the preferred chemotherapy regimen? And then what does the expert panel recommend regarding timing of interval cytoreductive surgery? Dr. Stéphanie Gaillard: Sure. So for neoadjuvant chemotherapy, we generally recommend a platinum taxane doublet. This is especially important for patients with high grade serous or endometrioid ovarian cancers, and that's really because this is what the studies had used in the neoadjuvant trials. We recognize, however, that sometimes there are individual patient factors, such as advanced age or frailty, or certain disease factors such as the stage or rare histology that may shift what is used in terms of chemotherapy, but the recommendation is to try to stick as much as possible to the platinum taxane doublet. And then in terms of the timing of interval cytoreductive surgery, this was something that the panel discussed quite a bit and really felt that it should be performed after four or fewer cycles of neoadjuvant chemotherapy, especially in patients who've had a response to chemotherapy or stable disease. Sometimes alternative timing of surgery can be considered based on some patient centered factors, but those really haven't been prospectively evaluated. The studies that looked at neoadjuvant chemotherapy usually did the interval cytoreductive surgery after three or four cycles of chemotherapy. Brittany Harvey: For those patients who are receiving interval cytoreductive surgery, Dr. Tew, earlier in the podcast episode, you mentioned a new therapy. What is recommended regarding hyperthermic intraperitoneal chemotherapy? Dr. Bill Tew: Yeah, or simply HIPEC as everyone refers to it. You know, HIPEC isn't really a new therapy. HIPEC is a one-time perfusion of cisplatin, which is a chemotherapy that has been a standard treatment for ovarian cancer for decades. But the chemotherapy is heated and used as a wash during the interval cytoreductive surgery. And since our last guideline, there has been a publication of a randomized trial that looked at the use of HIPEC in this setting. And in that study there was improved disease-free and overall survival among the patients that underwent HIPEC versus those that did not. So we wanted to at least emphasize this data. But we also wanted to recognize that HIPEC may not be available at all sites. It's resource-intensive. It requires a patient to be medically fit for it, particularly renal function and performance status. And so it's something that could be discussed with the patient as an option in the interval cytoreductive surgery. One other point, the use of HIPEC during primary surgery or later lines of therapy still is unknown. And the other point is this HIPEC trial came prior to the introduction of maintenance PARP inhibitors. So there's still a lot of unknowns, but it is a reasonable option to discuss with appropriate patients. Brittany Harvey: I appreciate you reviewing that data and what that updated recommendation is from the panel. So then, Dr. Gaillard, after patients have received neoadjuvant chemotherapy and interval cytoreductive surgery, what is the post ICS chemotherapy recommended? Dr. Stéphanie Gaillard: The panel recommends some post ICS chemotherapy, as you mentioned. This is typically to continue the same chemotherapy that was done as neoadjuvant chemotherapy and so preferably platinum and taxane. And typically we recommend a total of six cycles of treatment, although the exact number of cycles that is given post-surgery can be adjusted based on different patient factors and their response to treatment. Importantly, also, timing is a factor, and we recommend that postoperative chemotherapy begin within four to six weeks after surgery, if at all feasible. Brittany Harvey: Absolutely. Those timing recommendations are key as well. So then, Dr. Tew, you mentioned this briefly earlier, but what is the role of maintenance therapy? Dr. Bill Tew: Maintenance therapy could be a full podcast plus of discussion, and it's complicated, but we did want to include it in this guideline in part because the determination of whether to continue treatment after completion of surgery and platinum based therapy is key as one is delivering care in the upfront setting. So first off, when we say maintenance therapy, we are typically referring to PARP inhibitors or bevacizumab. And I would refer listeners to the “ASCO PARP Inhibitor Guideline” that was updated about two years ago, as well as look at the FDA-approved label indications. But in general, PARP inhibitors, whether it's olaparib or niraparib, single agent or olaparib with bevacizumab, are standard treatments as maintenance, particularly in those patients with a germline or somatic BRCA mutation or those with an HRD score positive. And so it's really important that we emphasize germline and somatic BRCA testing for all patients with newly diagnosed ovarian cancer so that one can prepare for the use of maintenance therapy or not. And the other point is, as far as bevacizumab, bevacizumab is typically initiated during the chemotherapy section of first-line treatment. And in the guidelines we gave specific recommendations as far as when to start bevacizumab and in what patient population. Brittany Harvey: Great. Yes. And the PARP inhibitors guideline you mentioned is available on the ASCO guidelines website and we can provide a link in the show notes for our listeners. So then, the last clinical question, Dr. Gaillard, what treatment options are available for patients without a clinical response to neoadjuvant chemotherapy? Dr. Stéphanie Gaillard: Yeah, this is a tough situation. And so it's important to remember that ovarian cancer typically does respond to chemotherapy initially. And so it's unusual to have progressive disease to neoadjuvant chemotherapy. So it's really important that if someone has progressive disease that we question whether we really have the right diagnosis. And so it's important to, I think at that point, obtain another biopsy and make sure that we know what we're really dealing with. In addition, this is where Dr. Tew mentioned getting the molecular profiling and genetic testing early in the course of disease. If that hasn't been done at this point in time, it's worth doing that in this setting so that that can also potentially help guide options for patients. And patients who are in those situations, really, the options are other chemotherapy regimens, clinical trials may be an option, or in some situations, if they have really rapidly progressing disease that isn't amenable to further therapy, then initiation of end-of-life care would be appropriate. Brittany Harvey: I appreciate you both for reviewing all of these recommendations and options for patients with advanced ovarian cancer. So then to wrap us up, in your view, what is both the importance of this guideline update and how will it impact clinicians and patients with advanced ovarian cancer? Dr. Bill Tew: Well, first off, I'm very proud of this guideline and the panel that I work with and Dr. Gaillard, my co-chair. The guideline really pulls together nicely all the evidence in a simple format for oncologists to generate a plan and determine what's the best step for patients. The treatment of ovarian cancer, newly diagnosed, is really a team approach - surgeons, medical oncologists, and sometimes even general gynecologists - and understanding the data is key, as well as the advances in maintenance therapy and HIPEC. Dr. Stéphanie Gaillard: For my part, I'd say we hope that the update really provides physicians with best practice recommendations as they navigate neoadjuvant chemotherapy decisions for their patients who are newly diagnosed with ovarian cancer. There is a lot of data out there and so we hope that we've synthesized it in a way that makes it easier to digest. And along that regard, I really wanted to give a special shout out to Christina Lacchetti, who just put in a tremendous effort in putting these guidelines together and in helping to coordinate the panel. And so we really owe a lot to her in this effort. Dr. Bill Tew: Indeed. And ASCO, as always, helps guide and build a great resource for the oncology community. Brittany Harvey: Absolutely. Yes, we hope this is a useful tool for clinicians. And I want to thank you both for the large amount of work you put in to update this evidence-based guideline. And thank you for your time today, Dr. Gaillard and Dr. Tew. Dr. Stéphanie Gaillard: Thank you. Dr. Bill Tew: Thank you for having us. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/gynecologic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.
Dr. Evan Yu presents the new evidence-based guideline on genetic testing for metastatic prostate cancer. He discusses who should receive germline and somatic testing with next-generation sequencing technologies, what samples are preferred for testing, and the therapeutic & prognosistc impacts of genetic testing. Dr. Yu emphasizes the need for awareness and refers to areas of active investigation and future research to improve personalized therapies for patients with metastatic prostate cancer. Read the full guideline, “Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline” at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02608 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Evan Yu from the University of Washington and Fred Hutchinson Cancer Center, lead author on “Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline”. Thank you for being here today, Dr. Yu. Dr. Evan Yu: Thanks for having me on. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the entire guideline, including Dr. Yu, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, Dr. Yu, to start us off on the content of this guideline, could you first provide an overview of both the purpose and scope of this guideline? Dr. Evan Yu: Yeah, absolutely. So I think the one key thing to recognize is that prostate cancer is the highest incidence of all cancers in males. Additionally, it's the second highest cause of mortality in males, and that's about 35,000 deaths in 2024. So with that being said and done, it's a disease where we need to do better. And part of that is recognizing that we now have many targeted therapies, precision medicine type of therapies, but unlike a lot of other cancers out there, prostate cancer patients are not always getting sequencing, next generation DNA sequencing, let's say, to identify both inherited and also spontaneously develop what we call somatic mutations in their tumor. And I suspect that's partially because other cancers like breast cancer, we're so used to- in the first line, you present the patient, you throw out their estrogen receptor status, progesterone receptor status, HER2, ER/PR HER2; in lung cancer it's EGFR, ALK, ROS1, etc. In things like prostate cancer, things like BRCA2 have major important patient treatment implications and potentially family counseling and downstream cascade testing implications. But it hasn't made their way into that first-line presentation yet. And for that reason, there are some studies out there that show that testing in the community may be as low as 15% of patients with metastatic prostate cancer. We want to bring awareness to that and hopefully increase testing down the road so that we can better help our patients with metastatic prostate cancer. Brittany Harvey: Absolutely. It's important to get these targeted therapies to the patients who can benefit most. Using that context, I'd like to next review the key recommendations of this guideline across the six clinical questions that the panel addressed. So, starting with: Who should receive germline testing with next generation sequencing technologies? Dr. Evan Yu: Yeah. We think that it's common enough that everyone with metastatic prostate cancer should receive germline genetic testing. And the reason for that is there have been studies that have looked at this and have shown that 12% of men with metastatic prostate cancer have some sort of inherited germline mutation in a gene, mostly DNA repair genes. But 12% have something that is inherited and that loved ones, first degree relatives, siblings, offspring might have also inherited. Now, most of these are in the DNA repair genes, but that being said and done, there's not only treatment implications for the patient, where there are newer drugs that that patient could get treated with, but other loved ones that might have inherited these gene mutations, that these things can cause other cancers as well - not just prostate cancer, but breast cancer, endometrial cancer, ovarian cancer, pancreatic cancer. So, it's very important to test, with as high of an incidence as 12%, to test, and if you identify it in a patient, it's our job to talk to the patient about it and talk to them about the pros and cons of family counseling and talking to their loved ones and potentially having their loved ones get tested. Because if they test positive, then their doctors may want to know and may screen them very, very aggressively and differently for a whole host of other cancers. And the whole idea is you find the cancer very early and cure the patients before the cancer really takes hold and has the ability to spread so we can save a lot of lives down the road. Brittany Harvey: Absolutely. This germline testing is important not just for the patient, but has wider implications for their families as well, as you mentioned. So then, beyond those recommendations for germline testing, which patients should receive somatic testing with next-generation sequencing technologies? Dr. Evan Yu: So let's talk a little bit about somatic testing. So germline again, as we know, is inherited. The patient inherited it in every single cell in their body, then it becomes very easy, many of these are cancer predispositions for them to lose the other allele and then to have biallelic loss and then develop the cancer. Now, somatic just means it spontaneously occurred. Certainly, it's not going to occur in every cell in the body, but you can get one hit, lose one allele and then lose the other allele. And if that gene is truly carcinogenic and leading to that cancer, then that can have implications potentially for treatment as well. So we recommend that all patients with metastatic prostate cancer also undergo somatic next-generation sequencing testing. We recognize that at this point in time it's only those with metastatic castration-resistant prostate cancer or hormone-resistant prostate cancer, which is a later disease state where there are drugs that may target those mutations, for instance, like PARP inhibitors, but that early identification for a patient population that's fit and that can benefit from these therapies makes sense so that you know it's in place already and you have your treatments outlined and mapped out for the future. So we recommend it for everybody - somatic testing also for everyone with metastatic prostate cancer. Brittany Harvey: Understood. And then when patients are receiving that somatic testing, what is recommended for somatic testing? Primary tumor archival tissue? Fresh metastatic biopsy tissue? Or circulating tumor DNA testing? Dr. Evan Yu: We recommend that in the initial setting when you're first diagnosed, that archival tissue samples are fine and preferred. But circulating tumor DNA is good when there's no accessible archival tissue, or if the archival tissue, let's say, is very old and it's been sitting around for a long time, or you can't get it anymore because it's many years back when maybe a patient had a prostate needle biopsy. So if it's not accessible, then we recommend ctDNA. We believe that is preferred and also that ctDNA is recommended in a situation where you can't easily biopsy a metastatic site. Sometimes it's just not in a safe area to go after. Sometimes it's just a small lesion. So in general, we recommend tissue when available, and when we think that the tissue sample will yield clean results, if not, then we recommend doing ctDNA at that point in time. Brittany Harvey: So you have described who should get germline and somatic genomic testing. But what are the therapeutic impacts of this germline or somatic testing for single gene genetic variants? Dr. Evan Yu: We pulled this panel together and we met like every single month for like 12 months straight, and part of it was to review the literature. And as part of this literature review, we were able to pull a whole bunch of different trials. I think there was like 1713 papers we identified in the literature search. Eventually, we narrowed it down because with ASCO, we want to present the data with the highest level evidence, level 1 evidence, randomized controlled prospective data. And after reviewing 1713 papers, we narrowed it down to 14 papers. With those 14 papers, if you look at it, there are a lot of things that we think may have implications for treatment or prognosis, but we didn't feel was the highest level of evidence that we could support. So the things that have the highest level of evidence that we can support are certain DNA repair gene alterations, especially BRCA2, and treatment with PARP inhibitors because there are many PARP inhibitor prospective trials that show progression-free survival benefit and even overall survival benefit. And so that's the type of study that achieved the level of evidence that we could include. So I would say BRCA1 and BRCA2 highest level of evidence and PARP inhibitor use also is included in that. Brittany Harvey: Understood. I appreciate you reviewing those therapeutic options. So then, the last clinical question, which you just touched on briefly, but what are the prognostic impacts of germline and/or somatic testing? Dr. Evan Yu: Whenever you do testing, especially if you use panel testing, you find a lot of information. There's a lot of different mutations and some of which are VUSs (variants of unknown significance) where we don't quite know what it means yet, but we can track that, especially if it's germline. But with somatic, we find lots of things that have implications, but maybe just not treatment implications. A perfect example is p53. p53 is one of the most common tumor suppressor gene mutations on all cancers, but in prostate cancer they can occur and they can usually occur late, although there can even be germline inherited p53 alterations. There's no treatment that targets p53 right now, but we know that if you have a p53 mutation that those patients may have more aggressive disease and that prognostic information is important to give to the patient. And I think it's important for future clinical trial design and direction. So we do not recommend making treatment recommendations or changes based on these prognostic only biomarkers at this point in time. But we do recommend that, based on this, we can design intensification trials for those patients who have these poor risk biomarkers and de-intensification trials for patients who may have a good risk biomarker. So for instance, SPOP is a gene where we think these patients may have better outcomes, they might respond better to certain hormonal therapies like abiraterone. I say might because the level of evidence isn't quite there. But what I would say is that these prognostic only biomarkers, we just don't think they cut the mustard yet to be able to make treatment decisions. But we do think that they can drive counseling for the patient and potential selection and trial design for the future to say, “Okay. This is a patient population that has a more aggressive cancer. We need to be more aggressive in treating these patients.” “This patient population might have a less aggressive cancer. Maybe we can de-intensify and say side effects and quality of life may be better for the patients.” Brittany Harvey: Definitely. It's important for thinking through how to personalize care for these patients. So then you've talked about this a little bit in talking through the recommendations, but could you expand on what is the importance of this guideline and how it will impact both clinicians and patients with metastatic prostate cancer? Dr. Evan Yu: Yeah, I think the number one thing is awareness. I think the data's out there and people that are in my field, they know this. But by evidence of the fact that it's not first-line presentation lingo that everyone's talking about things like BRCA status, it means it hasn't necessarily disseminated all the way through. So it's increasing awareness of the fact that both germline and somatic alterations can occur and that these may have impacts on the patient for their treatment and their prognosis, and basically to increase testing for the future. I really think that in the future, there'll be other reasons that we may want to serially even retest and we may find that there may be mutations that develop as mechanisms of resistance that might guide therapy down the road. So we need to get people to start doing this for everyone with metastatic prostate cancer, because someday we might be doing it not just once, but over and over again. Brittany Harvey. Absolutely. We hope this guideline reaches a wide audience and that these recommendations can be put into practice. Finally, you've talked about how not all the data in the field has yet risen to the level of evidence that made it into the guidelines. So what are the outstanding questions in future research areas for both germline and somatic genomic testing for metastatic prostate cancer? Dr. Evan Yu: It was in our discussion, but it clearly- it's not common enough for there to be randomized prospective trials that would reach that level of evidence to make it in this guideline recommendation. But we all know that for any solid tumor, you can get mismatched repair deficiency, microsatellite instability leading to hypermutation or high tumor mutational burden. And that happens in maybe 3 to 5% of patients with metastatic prostate cancer as well. There is evidence and data that these patients can potentially benefit from immunotherapies like pembrolizumab. But again, it's just not common enough for there to be those randomized prospective controlled trials out there. But we mention it because we know it's FDA-approved across all the tumor types, so we felt like we have to mention it because that's something that has treatment implications for the patient. But also, I alluded to this earlier, I think an area of active investigation is the tried and true number one driver of prostate cancer, which is androgen receptor. Testosterone binds to androgen receptors, stimulates it. That's how androgen deprivation therapy works. That's how abiraterone and the amides like enzalutamide, apalutamide, darolutamide, that's how they all work. But even beyond that, we're starting to identify that maybe 15%, 20% of patients with metastatic castration resistant prostate cancer have androgen receptor mutations. And there are newer classes of therapies like androgen receptor degraders like CYP11A1 antagonist that lead to complete adrenal annihilation of other steroid hormones that might promiscuously stimulate these androgen receptor mutants. These things develop as mechanisms of resistance, and in the future, we might want to serially test- and that's an active area of investigation in the future, to say you've been treated, let's say, with androgen deprivation therapy and abiraterone for years. There are certain mutations that might develop as a resistance mechanism. We might need to serially test somebody because you didn't have that mutation earlier on, but later in the disease course you might. And then there might be a new drug X out there that we would want to use. Again, we need the data, we need the randomized prospective controlled trials, but they're happening out there. And somewhere down the road we may rewrite this guideline and have a lot more recommendations to add to it. Brittany Harvey: Yes, we'll look forward to more research in this field to better provide targeted therapies for patients with metastatic prostate cancer across the treatment paradigm. And we'll look forward to report outs from those trials that you mentioned. So I want to thank you so much for your work to develop this guideline and thank you for your time today, Dr. Yu. Dr. Evan Yu: Thank you so much. It's wonderful to be here today. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.
In this two-part episode of the Precision Medicine Podcast, host Karan Cushman continues her deep dive into prostate cancer care with expert guest Dr. William Oh, a leading genitourinary oncologist, Director of Precision Medicine at Yale Cancer Center and Chair of the American Cancer Society National Prostate Cancer Roundtable. Building on part one (episode 63), they explore the transformative role of precision medicine, advanced diagnostics, and targeted therapies—emphasizing the urgent need for greater awareness, understanding, and advocacy as prostate cancer continues to rise steadily. Karan opens the conversation by emphasizing the growing complexity of prostate cancer diagnostics and treatment. Dr. Oh discusses the wide array of diagnostic tools, from PSA tests and MRIs to the cutting-edge PSMA PET scan, which has revolutionized staging and treatment planning by providing detailed insights into cancer spread. He highlights how these tools are helping oncologists tailor treatment plans with unprecedented precision. The discussion shifts to molecular diagnostics, a burgeoning field that provides critical information about the aggressiveness of cancer. Dr. Oh explains how molecular tests, such as genomic profiling, are enabling personalized treatment decisions for prostate cancer patients, particularly those on the fence about options like surgery, radiation, or active surveillance. Karan and Dr. Oh also address disparities in access to these advanced diagnostics, underlining the need for wider implementation. Karan steers the conversation toward advancements in targeted therapies. Dr. Oh outlines breakthroughs in precision treatments, including PARP inhibitors for patients with BRCA mutations and the innovative LU-177-PSMA therapy, a “smart bomb” approach that targets cancer cells with remarkable specificity. He also explores the promise of immunotherapy, though he acknowledges its limited applicability for prostate cancer due to the disease's low mutational burden. The role of artificial intelligence in precision oncology is another key topic. Dr. Oh and Karan discuss how AI and machine learning are helping clinicians process complex data, from imaging to genomic profiles, to guide more informed treatment decisions. Dr. Oh envisions AI as an essential tool for streamlining oncology workflows while preserving the human connection between doctors and patients. Karan highlights the importance of effective communication in prostate cancer care, referencing a recent editorial co-authored by Dr. Oh. Together, they explore the need for more patient-centered terminology, such as replacing the term “castration-resistant prostate cancer” with “androgen deprivation-resistant prostate cancer,” to foster better understanding and improve patient experience. The episode concludes with a forward-looking discussion on clinical trials, the integration of new technologies like liquid biopsies, and the ongoing efforts to expand insurance coverage for biomarker testing. Dr. Oh emphasizes the critical role of collaboration, awareness, and education in advancing precision medicine and ensuring that patients benefit from the latest innovations. With Karan's thoughtful questions and Dr. Oh's expertise, this episode offers a comprehensive and accessible exploration of how precision medicine is reshaping the future of prostate cancer care. We hope you'll tune in to the series and share this important episode with others!
In this JCO Article Insights episode, Giselle de Souza Carvalho provides a summary on "Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies" by Bhardwarj, et al and "US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations" by Dilawari et al published in the Journal of Clinical Oncology. TRANSCRIPT Giselle Carvalho: Hello and welcome to JCO Article Insights episode for the December issue of the Journal of Clinical Oncology. I'm your host Giselle Carvalho, Medical Oncologist in Brazil focusing on breast cancer and melanoma skin cancers and one of the ASCO Editorial Fellows at JCO this year. Today, I will be discussing two articles. The first one is “Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies,” and the second one is the “US FDA Approval Summary on Capivasertib with Fulvestrant for HR-positive HER2-negative Locally Advanced or Metastatic Breast Cancer with PIK3CA/AKT1/PTEN Alteration.” As we know, 65% to 70% of all breast cancers are HR-positive HER2-negative and this is also the most common subtype of metastatic breast cancer. The current standard of care for frontline therapy of patients with luminal metastatic disease is a CDK4/6 inhibitor in combination with endocrine therapy. However, as new endocrine and targeted therapies gain approval, choosing the best systemic therapy upon disease progression after frontline therapy is a topic of ongoing debate. Nearly 40 to 50% of HR-positive breast cancers have actionable genomic alterations and molecular testing should be a routine recommendation for patients with metastatic HR-positive HER2-negative disease. This can be performed repeating tissue biopsy at the time of progression or from archival tissue. Treatment options after progression on CDK4/6 inhibitors include alpelisib in combination with fulvestrant in patients with PIK3CA mutant tumors as seen in the SOLAR-1 trial, or capivasertib with fulvestrant in patients with a tumor mutation in (PI3K)–AKT–PTEN pathway as seen in the CAPItello-291 study, which will be discussed further. In approximately 30% of patients, progression on frontline endocrine plus CDK4/6 inhibitor treatment is caused by endocrine resistance, frequently involving activating mutations in ESR1. For those tumors, elacestrant, an oral SERD is an option as demonstrated in the EMERALD trial. For patients with a BRCA mutation, PARP inhibitors represent another option. If no mutations are detected, everolimus, an mTOR inhibitor, can be used based on the BOLERO-2 results. The phase 2 MAINTAIN and PACE trials, along with the phase 3 postMONARCH trial support changing the endocrine therapy backbone with or without switching the CDK4/6 inhibitor. In less resourced areas, fulvestrant monotherapy is still an option to delay cytotoxic chemotherapy, though its efficacy is limited when used as a single agent. Finally, after progression on at least one line of chemotherapy, antibody drug conjugates including sacituzumab govitecan or trastuzumab deruxtecan may be an option. Now focusing on the PI3K AKT PTEN signaling pathway, activating mutations in PIK3CA and AKT1 and inactivating alterations in PTEN occur in approximately half of luminal breast cancers. In June 2023, the CAPItello-291 trial was published and treatment with fulvestrant plus capivasertib, a PTEN AKT inhibitor, demonstrated a 3.6 month PFS benefit compared to fulvestrant alone, regardless of the presence of AKT pathway alterations. However, for those with tumors without AKT pathway alteration, an exploratory analysis showed that although there was a numerical improvement in PFS, it did not meet statistical significance, indicating that the biomarker positive population primarily drove the positive results noted in the overall population. Therefore, capivasertib plus fulvestrant was approved by the US FDA in November 2023 exclusively for patients with PI3K/AKT1/PTEN tumor alterations after progression on an aromatized inhibitor with or without a CDK4/6 inhibitor. The approved schedule of capivasertib is slightly different from that of other agents used in breast cancer. It is 400 milligrams taken orally twice a day for four days per week every week in a 28-day cycle in combination with fulvestrant. Diarrhea, rash and hyperglycemia were the most commonly reported grade three or four adverse events in the interventional group. I would like to highlight that even though the CAPItello trial excluded patients with glycosylated hemoglobin levels higher than 8% or those diagnosed with diabetes who required insulin, hyperglycemia occurred in 19% of biomarker positive patients treated with capivasertib, with nearly 2% of this population experiencing grade 3 or 4 hyperglycemia and some patients experiencing life threatening outcomes such as diabetic ketoacidosis. By way of comparison, hyperglycemia of any grade was three times higher with alpelisib therapy in the SOLAR-1 trial, occurring in 64% of the patients and grade three or higher hyperglycemia was seen in 37% of the patients. Diarrhea was the most common treatment related adverse event experienced by 77% of the biomarker positive population. Prompt use of the antidiarrheal drugs when needed, such as loperamide must be encouraged as untreated diarrhea can lead to dehydration and renal injury. Cutaneous rash occurred in 56% of the biomarker positive population in the interventional group and 15% experienced a grade 3 or 4 rash. Nearly half of the patients with cutaneous adverse reactions required treatment and this was the leading reason for dose reduction of capivasertib. In the biomarker positive population, the improvement in medium PFS were 4.3 months by investigator assessment. Overall survival data from the CAPItello-291 trial is still immature, but quality of life data was recently published in September this year and was assessed by the 30 item QLQ C30 questionnaire and the QLQ BR23, the breast module. According to Oliveira et al, global health status and quality of life were maintained for a longer period with capivasertib fulvestrant than with placebo fulvestrant except for symptoms of diarrhea which were significantly worse in the capivasertib group. The median time of deterioration of global health status and quality of life was twice as long in the capivasertib group being almost 25 months versus 12 months in the placebo fulvestrant group. These data reinforced the use of capivasertib in combination with fulvestrant for the treatment of HR-positive HER2-negative advanced breast cancer patients with PIK3CA/AKT1/PTEN tumor alterations who have progressed after an aromatase inhibitor-based therapy with or without a CDK4/6 inhibitor. Thank you for listening to JCO Article Insights. This is Giselle Carvalho. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. See you next time. 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.
In part one of a two-part series on prostate cancer, the Precision Medicine Podcast addresses critical challenges as well as new advancements in prostate cancer, the second leading cause of cancer-related deaths in men. Host, Karan Cushman, is joined by Dr. William Oh, Director of Precision Medicine at Yale Cancer Center and Chair of the American Cancer Society National Prostate Cancer Roundtable. Together, they shed light on the complexities of prostate cancer and how early screening can address rising incidence rates and persistent disparities, particularly among African American men. Subscribe to get Part 2 delivered straight to your inbox.Prostate cancer currently affects one in eight men in the US, with African American men facing a one-in-six risk and 70% higher incidence rate than White men. These disparities extend to earlier onset and more aggressive disease presentations. Globally, the disease is the most frequently diagnosed cancer in 112 countries and a leading cause of cancer-related deaths in 48 countries. The incidence of prostate cancer has been rising steadily. There has been a 3% annual increase in cases and a 5% annual rise in advanced prostate cancer diagnoses since 2014. Throughout the series, Dr. Oh discusses the role precision medicine can play in addressing these trends by tailoring prevention, diagnosis and treatment strategies to individual patient profiles. Karan and Dr. Oh begin the conversation by highlighting critical advances in prostate cancer care, including the development of over a dozen FDA-approved drugs in recent decades. Listeners will learn of the systemic barriers that often prevent men from accessing these treatments, resulting in just half of men with advanced prostate cancer receiving standard-of-care therapies—a fact that underscores the need to improve access and equity in treatment. Dr. Oh chairs the American Cancer Society National Prostate Cancer Roundtable, which aims to address these gaps by uniting diverse stakeholders—from patient advocacy groups to scientific organizations—to improve outcomes through collaborative efforts. The discussion also explores the role of environmental and epigenetic factors in prostate cancer risk. Dr. Oh discusses how stress, socioeconomic disparities, and toxic exposures, such as those experienced by 9/11 first responders, may alter DNA and increase cancer risk. He compares these findings to the higher incidence of prostate cancer among African American men who live in environments that exacerbate health disparities. Dr. Oh emphasizes the importance of identifying and mitigating these risks to improve outcomes. Screening is a key topic throughout the conversation, and Dr. Oh discusses the challenges of early detection and the controversies surrounding PSA (prostate-specific antigen) screening. While current guidelines recommend baseline PSA testing for most men between the ages of 50 to 55, new evidence supports earlier screening for high-risk populations, particularly African American men who should begin testing between ages 40 and 45. This shift toward earlier detection is critical for addressing aggressive cancers before they progress to advanced stages. Dr. Oh goes on to explain the importance of genetic testing, which reveals up to 10% of advanced prostate cancer cases involve BRCA or other DNA repair mutations. Recognizing these mutations early can inform targeted treatments like PARP inhibitors, yet Dr. Oh notes that many patients are not tested, underscoring the need for better implementation of precision diagnostics. By linking genetic data to clinical outcomes, precision medicine can help tailor treatments to the unique needs of each patient. The episode concludes with a call to action for improved education and collaboration. Dr. Oh emphasizes the need for patients to discuss family history and risk factors with their doctors and for primary care physicians to prioritize early conversations about prostate health. He advocates for a comprehensive approach that combines education, technology and multidisciplinary care to close gaps in prostate cancer treatment and ensure that advances in precision medicine benefit all populations, especially those at highest risk. Stay tuned for Part 2 with Dr. Oh coming out in late December 2024.
This is a conversation with Nicole Andrews, a patient with LGSOC and STAAR Ovarian Cancer Foundation Board Chairperson, and Dan Paterson, President and CEO of Verastem Oncology. Low-grade serous ovarian cancer is a rare and slow-growing ovarian cancer that is often misdiagnosed. Verastem Oncology is developing a targeted treatment for LGSOC and working with the STAAR Foundation to inform researchers about the disease and ways to improve treatments. Nicole was finally diagnosed with LGSOC after 18 months of unexplained symptoms, and her role at the STAAR Foundation is to raise awareness and funds to support research. Nicole explains, "I have since learned that low-grade is difficult for pathologists who aren't used to seeing it and don't know the intricacies of diagnosing. My surgeon finally said I have to get this right because it changes treatment." "So, she asked permission to send this to a specialty cancer center. And we did. Once that happened, they came back pretty quickly and said this was low-grade serous ovarian cancer. They were used to seeing it. They had high volume cases of reading pathology reports and, therefore, were able to diagnose and diagnose it." Dan elaborates, "The majority of ovarian cancers are so-called high-grade, and that's when you hear about treatment with chemotherapies like platinum. A new class of drugs called PARP inhibitors came out in the last couple of years. And I think when you generally hear about ovarian, it's high grade. It was only in the last couple of years that the World Health Organization and, more recently, the FDA, based on some of our work, recognized it as a distinct and different disease because it acts very differently. It tends to occur in younger women, and it's slower growing, which, on the face of it, you would think is a good thing. And I think a lot of times, and we've heard anecdotes, and Nicole can probably speak to this, where women have said, oh, well, you have the good ovarian cancer. The downside of a slower-growing tumor is it's harder to treat." #VerastemOncology #STAARFoundation #LGSOC #LGSOCAwareness #LowGradeSerousOvarianCancer #Cancer #RareDisease verastemoncology.com STAAR Foundation Download the transcript here
This is a conversation with Nicole Andrews, a patient with LGSOC and STAAR Ovarian Cancer Foundation Board Chairperson, and Dan Paterson, President and CEO of Verastem Oncology. Low-grade serous ovarian cancer is a rare and slow-growing ovarian cancer that is often misdiagnosed. Verastem Oncology is developing a targeted treatment for LGSOC and working with the STAAR Foundation to inform researchers about the disease and ways to improve treatments. Nicole was finally diagnosed with LGSOC after 18 months of unexplained symptoms, and her role at the STAAR Foundation is to raise awareness and funds to support research. Nicole explains, "I have since learned that low-grade is difficult for pathologists who aren't used to seeing it and don't know the intricacies of diagnosing. My surgeon finally said I have to get this right because it changes treatment." "So, she asked permission to send this to a specialty cancer center. And we did. Once that happened, they came back pretty quickly and said this was low-grade serous ovarian cancer. They were used to seeing it. They had high volume cases of reading pathology reports and, therefore, were able to diagnose and diagnose it." Dan elaborates, "The majority of ovarian cancers are so-called high-grade, and that's when you hear about treatment with chemotherapies like platinum. A new class of drugs called PARP inhibitors came out in the last couple of years. And I think when you generally hear about ovarian, it's high grade. It was only in the last couple of years that the World Health Organization and, more recently, the FDA, based on some of our work, recognized it as a distinct and different disease because it acts very differently. It tends to occur in younger women, and it's slower growing, which, on the face of it, you would think is a good thing. And I think a lot of times, and we've heard anecdotes, and Nicole can probably speak to this, where women have said, oh, well, you have the good ovarian cancer. The downside of a slower-growing tumor is it's harder to treat." #VerastemOncology #STAARFoundation #LGSOC #LGSOCAwareness #LowGradeSerousOvarianCancer #Cancer #RareDisease verastemoncology.com STAAR Foundation Listen to the podcast here
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/CPE information, and to apply for credit, please visit us at PeerView.com/VPZ865. CME/CPE credit will be available until December 10, 2025.Optimizing PARP Inhibitor Therapy in Veterans With Prostate Cancer: A Practical Guide for VA Pharmacists In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/CPE information, and to apply for credit, please visit us at PeerView.com/VPZ865. CME/CPE credit will be available until December 10, 2025.Optimizing PARP Inhibitor Therapy in Veterans With Prostate Cancer: A Practical Guide for VA Pharmacists In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/CPE information, and to apply for credit, please visit us at PeerView.com/VPZ865. CME/CPE credit will be available until December 10, 2025.Optimizing PARP Inhibitor Therapy in Veterans With Prostate Cancer: A Practical Guide for VA Pharmacists In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/CPE information, and to apply for credit, please visit us at PeerView.com/VPZ865. CME/CPE credit will be available until December 10, 2025.Optimizing PARP Inhibitor Therapy in Veterans With Prostate Cancer: A Practical Guide for VA Pharmacists In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits. To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits. To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits. To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/ILNA information, and to apply for credit, please visit us at PeerView.com/EFK865. NCPD/ILNA credit will be available until November 29, 2025.Nurse-Led Strategies for Optimizing PARP Inhibitors in Veterans With Prostate Cancer: Genomic Testing and Practical Care Delivery In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/ILNA information, and to apply for credit, please visit us at PeerView.com/EFK865. NCPD/ILNA credit will be available until November 29, 2025.Nurse-Led Strategies for Optimizing PARP Inhibitors in Veterans With Prostate Cancer: Genomic Testing and Practical Care Delivery In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/ILNA information, and to apply for credit, please visit us at PeerView.com/EFK865. NCPD/ILNA credit will be available until November 29, 2025.Nurse-Led Strategies for Optimizing PARP Inhibitors in Veterans With Prostate Cancer: Genomic Testing and Practical Care Delivery In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/ILNA information, and to apply for credit, please visit us at PeerView.com/EFK865. NCPD/ILNA credit will be available until November 29, 2025.Nurse-Led Strategies for Optimizing PARP Inhibitors in Veterans With Prostate Cancer: Genomic Testing and Practical Care Delivery In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and ZERO Prostate Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.
In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Drs. Anne Knisely and Nitecki Wilke to discuss Racial and Sociodemographic Disparities with Novel Therapeutics. Dr. Knisely is a 3rd year gynecologic oncology fellow at MD Anderson Cancer Center. She is originally from the New York City area and completed her residency training in Ob/Gyn at Columbia University in 2022 where Dr. Jason Wright served as her primary research mentor. Her current research focuses on early phase clinical trials, minimal residual disease in ovarian cancer, and sociodemographic factors that affect oncologic treatment and outcomes. She is a current SGO/GOG-F BRIDGES Research Scholar. In her free time, she mostly chases around her two toddlers, Zoe (3.5) and Isaiah (2). Dr. Nitecki Wilke is a gynecologic oncologist and assistant professor at the department of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center. Highlights: Of the 6242 patients who met inclusion criteria and were included in the final cohort, 4.4% received a PARP inhibitor, 34% received bevacizumab, and 6% received both. On multivariable analysis, non-Hispanic Black patients were 23% less likely than non-Hispanic white patients to receive either targeted therapy Most patients in the study were treated in the recurrent setting; we suspect that the potential barriers to guideline-concordant prescription of these therapeutics would persist in the upfront treatment setting, but future studies are required to validate this. A key area of focus to reduce disparities in access to targeted therapies should be ensuring adequate reimbursement for genetic/ biomarker testing as well as brainstorming creative solutions to expand access to genetic counseling, including the use of mainstreaming. Use of the SEER-Medicare database specifically reduces external validity of this study, but the results are nonetheless hypothesis generating and should spark conversation regarding potential inequitable receipt of PARP inhibitors and bevacizumab in advanced ovarian cancer
In this episode of the Oncology Brothers podcast, hosts Drs. Rahul and Rohit Gosain welcome Dr. Martina Murphy, an Associate Professor of Medicine and Senior Associate Dean of Graduate Medical Education at the University of Florida, to discuss the current landscape of ovarian cancer. Join us as we dive into the critical aspects of diagnosing and managing ovarian cancer, including: • The importance of surgical staging and primary debulking surgery • The role of genetic testing, including BRCA and NGS, in treatment planning • Adjuvant therapy options, focusing on platinum-based chemotherapy and the use of Bevacizumab • Insights into PARP inhibitors and their application in BRCA-positive and wild-type patients • Navigating treatment options for relapsed and refractory ovarian cancer, including the use of antibody-drug conjugates like Mirvetuximab and Trastuzumab Deruxtecan (TDXd). Dr. Murphy shares her expertise on the latest advancements in ovarian cancer treatment, the significance of genetic testing, and the management of side effects associated with various therapies. Tune in for a comprehensive overview of the standard of care for ovarian cancer and the evolving treatment landscape. Don't forget to check out our other episodes for more discussions on practice-changing data and current treatment options in oncology! Subscribe to the Oncology Brothers podcast for more insights and updates in the field of oncology! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com
In this JCO Precision Oncology Article Insights episode, Mitchell Elliot summarizes the article “Talazoparib in Patients With Solid Tumors With BRCA1/2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study” by Dr. Jordan Srkalovic et al. published on June 12th, 2024. TRANSCRIPT Mitchell Elliott: Hello, welcome to JCO Precision Oncology Article Insights. I'm your host Mitchell Elliott, an ASCO Journals Editorial Fellow. Today I'll be providing a summary of the article titled, “Talazoparib in Patients With Solid Tumors With BRCA1/ 2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study,” by Dr. Jordan Srkalovic et al. The Targeted Agent and Profiling Utilization Registry Study is a phase 2 basket trial evaluating the anti-tumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1 and 2 mutations treated with talazoparib are reported. BRCA1 is involved in both non homologous end joining, and homologous recombination, while BRCA2 primarily facilitates homologous recombination. These mutations are present in a range of cancers including breast, ovarian and pancreatic cancers, making them key targets for therapies that inhibit poly (ADP-ribose) polymerase or PARP, a family of proteins critical for DNA repair. PARP inhibitors like talazoparib have shown promise in treating cancers with BRCA mutations as they prevent tumors from repairing DNA damage, thus promoting cell death. Many PARP inhibitors are standard of care in both early and advanced cancers. Talazoparib was previously FDA approved for BRCA related HER2 negative breast cancer and prostate cancer. The TAPUR study aims to investigate the effectiveness of talazoparib and other types of solid tumors with BRCA1 and 2 mutations to expand its potential therapeutic applications. Eligible patients had to meet both general and drug specific criteria for inclusion in the study. General eligibility required participants to have advanced or metastatic solid tumors measurable by the RECIST version 1.1 criteria, a performance status of 0 to 2 based on the Eastern Cooperative Oncology Group Scale, and a genomic target identified through certified laboratory testing. Patients with germline or somatic BRCA1 or 2 mutations were eligible, but the genomic test did not always differentiate between these types of mutations. Additional criteria included being age 18 years or older, using effective contraception and avoiding sperm donation at the set period. Exclusion criteria included patients with HER2 negative breast cancer, prior PARP inhibitor treatments, or certain cardiovascular conditions. The study also excluded patients with recent major surgeries, coagulopathy and serious medical conditions, but there were no criteria related to prior platinum therapies. Patients received 1 milligram of talazoparib daily until disease progression, unacceptable toxicity, or other reasons for discontinuation. The primary endpoint of the study was disease control which was defined by achieving either objective response or stable disease lasting at least 16 weeks as assessed by the RECIST criteria. Secondary endpoints included objective response, progression free survival, overall survival, duration of response, duration of stable disease, and safety. The study enrolled 28 eligible patients with 20 different solid tumors that had BRCA1/2 alterations between December 2019 and September 2021 across 19 clinical sites with most patients, about 89%, enrolled from community-based locations in the United States. The most common tumor type was non-small cell lung cancer accounting for 18% of cases. All patients were included in both the safety and efficacy analyses including three with HER2 negative breast cancer and somatic BRCA alterations. Of the 28 patients, nine had tumors with BRCA1 alterations, 16 had BRCA2 alterations and three had both BRCA1 and BRCA2 alterations. Additionally, 64% of patients had tumors with coalterations and at least one DNA damage repair gene. In the study, one patient achieved a complete response, nine patients had partial response and six patients had stable disease for at least 16 weeks. The overall disease control rate was 57% with an objective response of 36%. The study rejected the null hypothesis of a 15% disease control rate with high statistical significance with a p-value of less than 0.001. The median progression free survival was 24 weeks and median overall survival was 71 weeks. Interestingly, among the 19 patients who received prior platinum-based chemotherapy, 5, or about 26%, had a partial response and 4 had stable disease while on talazoparib. While platinum therapy exposure can be associated with BRCA reversion mutations, it is notable that these patients achieve stable disease with PARP inhibitor treatment. 46% of the 28 patients experienced grade 3 - 5 adverse events or serious adverse events that were possibly related to talazoparib. 14% of patients had possible drug related serious adverse events which included conditions such as anemia, neutropenia, leukopenia, nausea and vomiting. More severe grade 4 or 5 events included anemia, neutropenia, thrombocytopenia, leukopenia, hyponatremia, and increased level of the aspartate aminotransferase and bilirubin. In conclusion, this study demonstrates that talazoparib shows significant antitumor activity in patients with advanced solid tumors carrying both BRCA1 and BRCA2 mutations, even in cancers beyond those for which PARP inhibitors are currently FDA approved. The disease control and objective response rates indicate promising results in heavily pretreated patients who have no standard treatment options left. The findings suggest that PARP inhibitors like telazoparib could be effective in a broad range of cancers, including non-small cell lung cancer, mesothelioma and hepatocellular carcinoma where PARP inhibitors are not yet approved. This could pave the way for expanding the use of these drugs in precision oncology. While talazoparib showed efficacy, the study also reported a notable incidence of grade 3 to 5 adverse events, highlighting the need for careful management of side effects, particularly in heavily pretreated patients. The study calls for further research, particularly in randomized controlled trials to confirm the efficacy of talazoparib in other cancers beyond what is currently approved. It also suggests investigating the effect of DNA damage repair gene alterations and exploring combinations of PARP inhibitors with other targeted therapies. Additionally, further studies are needed to understand the potential differences in response between BRCA1 and BRCA2 mutations. Thank you for listening to JCO Precision Oncology Article Insights and please tune into the next topic. Don't forget to give us a rating and review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at www.asco.org/podcasts. 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.
Ovarian cancer, often referred to as the "silent killer," has been misunderstood for years. In this episode of 20-Minute Health Talk, Jill Whyte, MD, a leading gynecologic oncologist at Northwell Health, demystifies the subtle symptoms that frequently go unnoticed and emphasizes the critical role of early diagnosis — particularly for those at the highest risk of ovarian cancer. She also explores the latest advances in treatment, from targeted therapies like PARP inhibitors, to minimally invasive surgeries and new preventive strategies. Prophylactic fallopian tube removal has been the standard of care for those at the highest risk but is now being used in certain situations for women at average risk. During Ovarian Cancer Awareness Month in September, Dr. Whyte implores women everywhere to educate themselves and their family and friends to help reduce the impact of this deadly disease. Chapters: 01:15 - Ovarian cancer prevalence, trends 01:54 - Ovarian cancer symptoms 04:20 - PARP inhibitors and other ovarian cancer treatments 06:00 - Ovarian cancer risk factors 06:38 - Surgery types 08:38 - Strategies to prevent ovarian cancer 10:30 - The role of the fallopian tubes 14:50 - Catching ovarian cancer early 15:17 - Genetic testing 16:12 - Northwell's Cancer Institute 17:15 - Patient navigators Watch episodes of 20-Minute Health Talk on YouTube. For information on our more than 100 medical specialties, visit Northwell.edu and follow us @NorthwellHealth on Facebook, Instagram, X and LinkedIn. Interested in a career at Northwell Health? Visit http://bit.ly/2Z7iHFL and explore our many opportunities. Facebook – / northwellhealth Instagram - / northwellhealth X - https://www.x.com/northwellhealth LinkedIn - https://www.linkedin/northwellhealth
In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Lot Aronson and Willemien van Driel to discuss OVHIPEC1 overall survival analysis. Dr. van Driel is a gynecological oncologist at the Netherlands Cancer Institute since 2004 and has, amongst others, a special interest in determining the role of HIPEC in the treatment of patients with advanced ovarian carcinoma and is PI of the OVHIPEC 1 and OVHIPEC 2 study. Dr. Aronson is a medical doctor currently pursuing a PhD in Gynaecological Oncology at the Netherlands Cancer Institute in Amsterdam. Her research focuses on hyperthermic intraperitoneal chemotherapy (HIPEC) as well as immunotherapy in primary advanced ovarian cancer. Highlights: The long-term survival analysis of the OVIHPEC-1 study confirms the significant improvement in progression-free and overall survival when adding HIPEC to interval cytoreductive surgery in patients with FIGO stage III ovarian carcinoma for whom primary cytoreduction is not considered feasible due to extensive disease. Neither the number of lines nor the type of subsequent treatment for recurrence differed between the treatment groups. Therefore, the observed improvement in overall survival is unlikely to be attributable a difference in subsequent therapies. Identification of biomarkers (e.g. BRCA/HRD status) to select patients for HIPEC and the combination of HIPEC with PARP inhibitors warrants further investigation.
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