Podcasts about Olaparib

Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul & Rohit Gosain are joined by Dr. Laura Huppert from UCSF to discuss key highlights from the San Antonio Breast Cancer Symposium 2024. We dive into three crucial studies: 1.⁠ ⁠INSEMA Study: Explore the findings on the potential omission of axillary surgery in early-stage hormone receptor-positive breast cancer and its implications for patient quality of life. 2.⁠ ⁠KEYNOTE-522 Update: Learn about the latest insights on the use of Pembrolizumab in triple-negative breast cancer, including the search for predictive biomarkers and the impact of achieving pathological complete response (PCR). 3.⁠ ⁠OlympiA Study Update: Discover the updated results on the use of Olaparib in BRCA-positive patients, highlighting its significant benefits in invasive disease-free survival and overall survival. Join us as we unpack these important studies and their implications for clinical practice. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

In this episode, listen to Floor J. Backes, MD, and Angeles Alvarez Secord, MD, MHSc, share their clinical insights and takeaways on new data presented for endometrial, ovarian, and cervical cancers presented at the 2024 annual meetings of the Society of Gynecologic Oncology and American Society of Clinical Oncology including:RUBY Part 1 Subgroup Analyses by MRR Status: Addition of dostarlimab to platinum-based therapy followed by dostarlimab maintenance in advanced endometrial cancerRUBY Part 2: Survival outcomes with addition of dostarlimab to platinum-based therapy followed by dostarlimab plus niraparib maintenance in advanced endometrial cancerSurvival Analyses From Phase III NRG GY018: Carboplatin plus paclitaxel with or without pembrolizumab as frontline treatment for patients with advanced endometrial cancerDUO-E: First-line therapy with carboplatin plus paclitaxel plus bevacizumab and durvalumab followed by maintenance with bevacizumab, durvalumab, and olaparib in newly diagnosed endometrial cancerLong-term Follow-up From SIENDO: PFS in TP53 wild-type and preliminary survival by molecular subgroups in patients with endometrial cancer and complete or partial response after ≥12 weeks of first line taxane/carboplatinSubgroup Analyses From the Randomized Phase III MIRASOL: Mirvetuximab soravtansine vs investigator's choice of chemotherapy in FR

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

You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, members of the Cancer.Net Editorial Board discuss the latest research, innovations, and discussions taking place across the field of genitourinary cancers, including prostate cancer, bladder cancer, kidney cancer, and testicular cancer. This podcast is led by Cancer.Net Associate Editor for Genitourinary Cancers, Dr. Petros Grivas. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine and a professor in the clinical research division at the Fred Hutchinson Cancer Research Center. He is joined by Dr. Neeraj Agarwal, Dr. Shilpa Gupta, Dr. Tian Zhang, and Dr. Timothy Gilligan. Dr. Agarwal is a Professor of Medicine, and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute at the University of Utah. He directs the Genitourinary Oncology Program and Center of Investigational Therapeutics at the Huntsman Cancer Institute. He is also the Cancer.Net Specialty Editor for Prostate Cancer. Dr. Gupta is the Director of the Genitourinary Medical Oncology Program at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. She is also the Cancer.Net Specialty Editor for Bladder Cancer. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also the Cancer.Net Specialty Editor for Kidney Cancer. Dr. Gilligan is a Medical Oncologist, Associate Professor of Medicine, and Vice-Chair for Education at the Cleveland Clinic Taussig Cancer Institute. He is also the Cancer.Net Specialty Editor for Testicular Cancer.  View full disclosures for Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan at Cancer.Net. Dr. Grivas: Hello. I'm Dr. Petros Grivas. I'm a medical oncologist in Seattle, a professor at the University of Washington and Fred Hutchinson Cancer Center. I'm really excited and thrilled today to host wonderful superstars in the field of GU Medical Oncology who will share insights about the highlights of kidney cancer, prostate cancer, and bladder, urothelial, urinary tract cancers that happened in 2023. And this highlight aims to inform our great audience about what are the clinically relevant insights, what patients should be aware, what patients should ask for when they go to the clinic, or overall, how they can be most well-informed and have the necessary tools to improve their care and feel well-supported in regards to education. So without further ado, we're going to cover in first prostate cancer, a very important update in this year. So all the people out there that are interested in hearing about prostate cancer will find this very, very useful and insightful. I'm very excited to host Professor, Dr. Neeraj Agarwal from University of Utah. Neeraj, do you want to introduce yourself? Dr. Agarwal: Of course. It's such an honor to be here. My name is Dr. Neeraj Agarwal. I'm a professor of medicine and director of genitourinary oncology program at the University of Utah Huntsman Cancer Institute. Dr. Grivas: Neeraj, thank you so much for accepting the invitation and being with us. I would like to ask you, what's your take on the current state of genetic testing in patients with prostate cancer? And when we say genetic testing, maybe you can clarify the distinction between germline and somatic and comment on both if you could. Thank you. Dr. Agarwal: Of course, a very important topic. I must tell you that it is very clear from all the guidelines that in patients with advanced prostate cancer or metastatic prostate cancer, meaning when prostate cancer has spread to different parts of the body, both germline testing to look for hereditary mutations in the DNA repair genes and testing for the same genes inside the tumor tissue are considered standard of care. So, a patient with advanced prostate cancer should have germline testing and somatic tumor tissue testing to look for mutations that can predispose them to have prostate cancer, and if they have genes in the tumor which can be targeted by the current approved drugs, like drugs which are already approved right now or which are in clinical trials. Unfortunately, less than 50% of patients in many areas of the country and in the world, less than 20% of patients are being tested. And even more, unfortunately, patients are less likely to be tested are those who are not well-resourced, who are not living in rich countries, if you will. They are poor- or low-resourced countries. Even with high-income countries, within those countries, patients who are living in relatively not-so-affluent neighborhoods, they are less likely to be tested. From racial perspective, patients who are Black or who are Hispanics are less likely to be tested. Based on how many drugs are out there in the clinic and emerging through clinical trials. And the fact that we can use many of these mutations for prognostication, to inform survival, to inform aggressiveness of the disease. It is not only to treat those patients, but also how to monitor the disease. The genetic testing is very important. Dr. Grivas: Thank you so much, Neeraj. It's very insightful. And I think you did a great job outlining the clinical relevance for both the patient in terms of treatment decision-making and therapy options, especially for advanced prostate cancer, as well as the broader family and implications for cancer prevention and cancer screening for the broader family members. So definitely a very important topic. Neeraj, the other question I have, if you could tell us more about this class of medications called PARP inhibitors. If you can comment on the currently approved PARP inhibitors, either as a single agent, what we call monotherapy or combination therapies for patients with prostate cancer in the United States, and who is eligible to receive those therapies? Dr. Agarwal: And this is such a nice segue to talk about PARP inhibitors as we were just talking about genetic testing of prostate cancer. So, PARP inhibitors are a class of drug which are instrumental, critical in treatment of patients who harbor mutations in those DNA repair genes. And two monotherapies, meaning using these PARP inhibitors as single agents have been already approved in the United States and several other countries. These are olaparib or rucaparib. Olaparib is approved after patients have had disease progression on novel androgen-blocking therapies or androgen blockers such as enzalutamide or abiraterone or apalutamide. And these PARP inhibitors such as olaparib or rucaparib can be used for those patients as single agent if they have these DNA repair mutations. Now, last year, we saw several combinations of PARP inhibitors with these androgen or novel hormonal therapy, as we call them. And these include abiraterone plus olaparib, abiraterone plus niraparib, and talazoparib plus enzalutamide from various phase 3 trials. Now, I'd like to bring to your attention that these PARP inhibitor combinations are approved with different indications in the United States and in the European Union. And they continue to get approved in various other countries. So the combination of abiraterone and a PARP inhibitor, whether it is olaparib or niraparib, they are approved for patients who have new metastatic castrate-resistant prostate cancer, and they have BRCA1 or BRCA2 mutations in the cancer cells or they have germline BRCA1 and BRCA2 mutations. Enzalutamide and talazoparib combination is approved in the United States for patients with metastatic castration-resistant prostate cancer with BRCA1 and BRCA2 mutations, but also several other DNA repair gene mutations. And that's a big difference as far as approval is concerned in the U.S. In the European Union, for our patients who are listening from European Union, the combination of abiraterone and olaparib and enzalutamide and talazoparib are approved for patients with metastatic castrate-resistant prostate cancer where chemotherapy is not clinically indicated, regardless of whether they have mutations in the DNA repair genes or not. And the combination of abiraterone and niraparib is only approved for patients with metastatic castrate-resistant prostate cancer with BRCA1 and BRCA2 mutation. So I just wanted to outline the different indications in the United States and in the Europe. Dr. Grivas: Thank you so much, Neeraj. So eloquent and very relevant to multiple patients globally, as you pointed out, with some differences in terms of the regulatory approval and availability of those agents in different countries. So great insights. Maybe we'll ask you 1 more question again since we are doing the highlights of the year. Another very important area of therapeutic development has to do with these novel agents that target the prostate cancer cells, and we call them theragnostics as a broader term. And I will let you explain what that means maybe in lay terms for our audience. And specifically, if you can comment on the recently presented PSMAforetrial at the ESMO meeting in Madrid with lutetium-177 PSMA. What are the implications of these results for our patients, and what is the role of lutetium therapy in this particular therapy setting? Dr. Agarwal: Of course, very important and pertinent topic indeed. As our patients may know that lutetium-177 therapy, or simply speaking, lutetium therapy, has already been approved for patients with metastatic castrate-resistant prostate cancer who have had disease progression on this novel hormonal therapy and a chemotherapy with docetaxel or cabazitaxel. And this indication is already there in the U.S. and in various other countries. And patients are eligible to receive lutetium therapy as long as their disease has progressed on docetaxel or one of the taxane chemotherapy and a novel hormonal therapy. Now, in the European Society of Medical Oncology meeting, Dr. Oliver Sartor presented the data on PSMAfore trial where lutetium therapy was used before chemotherapy. In this trial lutetium therapy was compared with another novel hormonal therapy after disease progression on 1 novel hormonal therapy. And there was approximately 6-month improvement in progression-free survival, meaning there was a delay in disease progression by 5 to 6 months in patients who were receiving lutetium therapy. And at the time of the report, there was no improvement in overall survival, with the caveat that 84% patients who were receiving novel hormonal therapy, actually, they switched over to lutetium therapy after disease progression. So, overall, survival data may not be met. Having said that, we already know that lutetium therapy is an effective therapy, and it has a definitive role in treatment of our patients with metastatic castrate-resistant prostate cancer. Dr. Grivas: Thank you, Neeraj. That's very, very important data. And I'm so glad we have many more therapy options for our patients with prostate cancer. So involvement and accrual in clinical trials, I'm sure you will agree, is a very important and high priority. And I always encourage people with prostate cancer to ask about clinical trials that are relevant to their situation. Dr. Agarwal: Yeah. I'd just like to add a point regarding lutetium therapy that there was a phase 2 trial in from Australia which compared lutetium therapy with cabazitaxel therapy after disease progression and docetaxel chemotherapy. And efficacy of both agents were not very different. So just wanted to make that point. Dr. Grivas: Thank you, Neeraj. It's a very important point. And obviously, always want to think about pace and preference, convenience, distance from the cancer centers, all the relevant points, how we can individualize suggestions or recommendations for our patients. Thank you so much, Neeraj, for your wonderful input, insights, and all the work you do in the field. Dr. Agarwal: Thank you very much for having me. Dr. Grivas: Of course, of course. And now we're going to transition to a different cancer type. We're going to talk about bladder cancer and urothelial cancer in general, urinary tract cancer. And we're delighted and excited to have Dr. Shilpa Gupta from Cleveland Clinic, who's a professor there of oncology. Shilpa, I want to introduce yourself? Dr. Gupta: I'm Shilpa Gupta. I'm a genitourinary medical oncologist and the director of the GU Program at Cleveland Clinic. I'm really excited to be doing this podcast with you all. Dr. Grivas: Thank you, Shilpa. You have done amazing work in the field, pushing the field forward. You are part of those transformative studies. I will ask you in the beginning where I'm going to focus my first question for people who have advanced or metastatic bladder cancer or urinary tract cancer or upper or lower tract. And we saw really exciting, impressive data at the recent ESMO Congress in Madrid a couple of months ago. And I know you were there and were enjoying to see the improvement in patient outcomes that comes with better quality of life for patients in the last several years. And the question I have for you, if you want to summarize the key data in the first-line treatment, patients who have no prior treatment for metastatic urothelial cancer, what are the key data we showed at the ESMO meeting? Dr. Gupta: Thank you, Petros. As you said, this is a really exciting time for both patients as well as the physicians treating bladder cancer because of all the new developments which we've seen after decades. So at ESMO 2023, we saw the key data from the EV-302 trial, which was a phase 3 trial, which randomized patients to the standard of care, platinum-based chemotherapy, gemcitabine-cisplatin or gemcitabine-carboplatin, versus a novel drug, which is an antibody-drug conjugate called enfortumab vedotin and the immunotherapy pembrolizumab. And the primary endpoint was to see if patients lived longer and this delayed progression. And we saw that in this the progression-free survival, we saw that it was 12.5 months with enfortumab vedotin and pembrolizumab compared to 6.3 months, which means that the risk of progression or death was decreased by 55% with this new combination. And the benefit was seen across all the various factors, especially patients with liver metastases, visceral metastases, whether or not they had contraindications to receiving cisplatin or not or PD-L1 expression. So this is the first time we saw such a remarkable benefit with any treatment that beat platinums. And the overall survival was also doubled: 16 months in chemotherapy versus 31.5 months with this combination. So the risk of death was reduced by 53%. And we also saw that the overall response rates were 68% with this compared to 44% with chemo. And 29% of patients had complete responses. And this was really remarkable because we have not seen such data before. And in the same session, we also saw another phase 3 trial that was presented, which was the Checkmate 901 trial, in which the investigators tested whether the addition of immunotherapy called nivolumab to the standard of care, gemcitabine and cisplatin was better than gemcitabine and cisplatin alone. So this was a study only looking for patients who can receive cisplatin. So patients were randomized to 6 cycles of gemcitabine cisplatin versus nivolumab, gemcitabine cisplatin for up to 6 cycles. And after that, they continued nivolumab maintenance every month for up to 2 years. And in this, the primary endpoint of overall survival was also met, although the difference was not as huge as the other study. It was 18.9 months with chemotherapy versus 21.7 months with the combination. And progression-free survival was also improved by just 0.3 months with the combination. And the objective response rates were higher with the combination, 57% versus 43%, and there were 21% complete responses. So the bottom line is that both these trials showed us that the frontline treatment is not going to be just platinums anymore moving forward. We will have the option of the enfortumab vedotin and pembrolizumab for all comers, patients who can get platinums, and nivolumab and gemcitabine cisplatin for patients who are cisplatin eligible. Dr. Grivas: Thank you, Shilpa. Wonderful summary. Really, really exciting time to see the field moving forward and translate those results to longer life for our patients. In that context, I will also ask you—I asked Neeraj before about genetic testing in prostate cancer. I will ask you a similar question about genetic testing in bladder cancer. Again, reminding the audience about the distinction between germline testing, which is the DNA we are born with, and somatic testing, which is the cancer-specific genomic changes. Could you comment on the importance of genetic testing in bladder cancer? Dr. Gupta: Yes. Absolutely, Petros. Genetic testing in urothelial cancer is very important because for the first time a few years ago, we saw a drug targeting the fibroblastic growth factor receptor or FGFR alterations. This drug is called erdafitinib. It is the first targeted therapy to be approved in urothelial cancer. It is only seen in up to 20% of patients who harbor these alterations for whom this option may be viable. And we saw initially that erdafitinib was approved in patients who harbor these alterations in the phase 2 BLC2001 trial where it showed response rates of 40% and encouraging progression-free survival, and overall survival. And then we also saw in a phase 3 trial called the THOR trial where patients who harbored these alterations by genetic testing, erdafitinib was much better than chemotherapy, prolonged survival by almost 4.2 months compared to chemotherapy. So unless we are testing, we won't find this. So it is really important to test all our advanced disease patients so we are not depriving them of this additional targeted therapy. Dr. Grivas: Thank you, Shilpa. Very important message for our patients to definitely discuss the value of genetic testing. And if we think about therapy implications, specifically genomic changes, DNA changes in these FGFR-2 and FGFR-3 genes are very relevant and important for potential therapy with this agent called erdafitinib. Shilpa, a quick comment. We saw data from THOR cohort 2 comparing erdafitinib with this inhibitor of this FGFR that we just talked about compared to pembrolizumab, which is an immunotherapy drug inhibiting a checkpoint of the immune system. Could you quickly comment on that? And I think both options are available for our patients and sometimes just comes down to the sequence based on a particular patient case. Dr. Gupta: So Petros, as we had thought that patients who harbor these alterations in their tumors, they may benefit from using targeted therapy before immunotherapy. That was the premise of the cohort 2 of the THOR trial, that patients will do better if they received erdafitinib first after progressing on 1 prior line of therapy, which is not an immunotherapy. So patients were randomized to erdafitinib versus pembrolizumab. Of course, all of them had to have the FGFR alterations. The primary endpoint was overall survival. Initially, like I said, the study assumed that there'll be 46% improvement in overall survival with erdafitinib over pembrolizumab. However, the study was a negative study. There was no difference in the overall survival. And what that means for our patients is that erdafitinib right now is positioned for patients who've had prior platinums and immunotherapies. So erdafitinib should not be used before immunotherapy. So I think this is the first study that really settles the question of sequencing for our patients. And I think the message is that in a patient's journey, they should be getting all these therapies. We just now know that it's better to use pembrolizumab before erdafitinib and not vice versa. Dr. Grivas: Thanks, Shilpa. And then really, really interesting to see these trials being reported. And as you said, individual discussion with the patients and the response rate may be another factor to consider. If someone wants to have a more rapid control of the cancer of the disease, we may potentially think about an agent with high response rate and vice versa. So I think to your point, individual decisions. And I think patients asking those questions is very important in the clinic to help select the right patient for the right treatment for the right patient. Dr. Gupta: Yeah. Absolutely, Petros. They did see that the response rates were 40% with the erdafitinib versus 21% with the immunotherapy. So using that information can sometimes guide us if a patient has high disease burden. Dr. Grivas: Thank you, Shilpa. That was very insightful. And thank you for all you are doing for the patients and the field in general. You really, really have helped the field move forward. So congratulations and thank you. And we're going to transition to another superstar in the field of GU cancers. Very excited to host Dr. Tian Zhang. Dr. Zhang is in UT Southwestern in Dallas. Tian, you want to introduce yourself? Dr. Zhang: Hi, Petros. Thank you so much. Tian Zhang, I'm a GU medical oncologist and associate professor at UT Southwestern Medical Center in Dallas. Dr. Grivas: Wonderful. Thanks, Tian. Again, the same comments. All the work you're doing in the field is tremendous. Thanks for joining us today. Tian, we saw some very interesting data at the ESMO meeting. And since we're doing the highlights of the year, I think the predominance of the data we saw at the ESMO meeting was about this drug called belzutifan, where I will ask you to enlighten us what exactly this is. And particularly, we saw 3 different trials. I would probably ask you to focus more on the LITESPARK-005. What was the trial design and what was the primary goal of the study? When patients go on this drug, what they should be aware in terms of side effects? And what was all this discussion that the take-home message at the end of ESMO regarding belzutifan? Thank you. Dr. Zhang: Sure. We'll parse that one at a time. Belzutifan, I hope many of our audience knows is a small molecule inhibitor of the HIF complex, a hypoxia-inducible factor complex, which is implicated in the development of kidney cancers. And this biology actually contributed to the Nobel Prize in 2019. Understanding the structure of the HIF complex and how to target it. For a long time, HIF was thought to be un-targetable. And so the fact that there were small molecules identified actually here in Dallas at UT Southwestern that inhibits the dimerization of the HIF complex is really novel and shows us the bench-to-bedside translatability of these preclinical discoveries. And so there were a couple of molecules that were discovered here on campus and they paved the way for what became molecules that have now made it to clinic, in particular belzutifan. And so we've had belzutifan now approved for Von Hippel-Lindau Syndrome over the last 2 years or so. So many of us are familiar with using this drug in the clinic. It's an oral agent that's able to target the HIF complex and block it and really control the spread of clear cell kidney cancers, in particular in Von Hippel-Lindau disease.  LITESPARK-005, the trial that you're alluding to, there was a registrational trial for belzutifan across other kidney cancer populations. And this trial was the 1 that made, I think, the biggest impact of the 3 trials that were presented at ESMO this year.  LITESPARK-005 was a phase 3 trial of patients who had metastatic or locally advanced clear cell kidney cancer who had progressed after prior systemic therapies, not more than 3 prior lines. And they were randomized to either belzutifan at the 120 milligrams daily dose or everolimus at the 10 milligrams daily dose. And the primary endpoint was delay of progression. So progression-free survival as well as overall survival. So we saw the primary endpoint of these was met for progression-free survival. There was about a 26% risk reduction for progression for patients treated with belzutifan versus those that were treated with everolimus. The objective response rate I would highlight is also significant for the patients treated with belzutifan. There was actually a 3.5% complete response rate and objective responses. So including partial responders was about 23%. I would say that patients who are treated with belzutifan need to be aware of the side effects of anemia and also hypoxia [low levels of oxygen in the body]. And in fact, higher grades of anemia can occur in up to a third of patients and higher rates of hypoxia. So low oxygen saturations can occur in up to 10% or so of patients. And so that's really important when we're thinking about those toxicities and how we might hold or support the side effects with growth factors, for example, for the anemia. Otherwise, it's quite well tolerated as a single agent. As you alluded to, there was 1 controversial aspect of this particular trial because the control cohort was treated with everolimus. And everolimus as a single agent may not be what people use at this point in the refractory setting. But it is an acceptable approved treatment option for patients in the refractory kidney cancer setting, and therefore, it was chosen as the control cohort. And belzutifan did improve compared to a known standard of treatment. So I think that's really important to add to our armamentarium in refractory disease. Dr. Grivas: Wonderful, Tian. Thank you so much for a really, really comprehensive and detailed review. We'll have to see whether it will be available for patients with advanced clear-cell kidney cancer. To your point, it's already available for patients with this condition that you mentioned, the Von Hippel-Lindau genetic condition. So it's great to see more options available for our patients. Maybe I'll ask you another quick trial to comment on Tian, and I'll ask you individual questions to make it easier, to your point, for the audience to follow. And I'm referring to the RENOTORCH trial. This was conducted in China, and I think it was practice-changing there. Could you tell us the study design? Dr. Zhang: RENOTORCH was another phase 3 randomized trial. It was conducted all in China of patients with unresectable metastatic clear cell kidney cancer, no systemic prior therapy, and also intermediate- and poor-risk disease by IMDC criteria. So these were all first-line metastatic disease, and patients were randomized to either toripalimab, which is their PD-1 inhibitor, plus axitinib versus sunitinib. So this is a trial design that mirrors many of our prior trials in the first-line metastatic setting that have led to approvals of VEGF IO [immunotherapy] combinations. But this is the first one that was carried out purely in the Chinese population and important for the Chinese population to gain access to these types of combinations. Dr. Grivas: Thank you, Tian. Very important to see this global approach, as you mentioned, oncology and see trials from different countries. What were the main findings of this trial? Dr. Zhang: Sure. The primary endpoint was progression-free survival of the 2 cohorts. And they randomized about 420 patients. About 80% per cohort had intermediate-risk disease. And the combination of axitinib with toripalimab did improve progression-free survival. So it had a 35% risk reduction for progression over time. So it did meet its primary endpoint. Dr. Grivas: Thank you, Tian. It's great to see progress in the field. As I mentioned, new agents, positive trials. Could you comment a little bit on the side effect profile and the significance of this trial for our patients worldwide? Dr. Zhang: Sure. When we're talking about VEGF IO combinations very similarly as to the prior trials that we've seen in the toxicity profiles, we're thinking a lot about the immunotherapy toxicities of rashes and colitis [inflammation of the colon], endocrinopathies [hormone problems], as well as the rare inflammatory reactions of the liver, lungs, or kidney, but also added in the small molecule effects of hypertension, hand-foot syndrome, and mucositis [mouth sores] and taste changes. So very important to think through those side effect profiles as our patients are being treated with these combinations. Dr. Grivas: Thank you so much, Tian. Great to see, again, this progress made worldwide. And I think it speaks to the idea of how we can have equitable healthcare delivery across the globe, right, and have agents accessible in different parts of the world. Dr. Zhang: Absolutely. In fact, I would just add that the Chinese population haven't actually had access to drugs like cabozantinib. And this is their first phase 3 grade 1 evidence for a combination of VEGF with IO combination. So it's really important that these trials are carried out in the populations where we try to find the effect and see that the consistent benefit is there so that those patients have access to all of these treatment options. Dr. Grivas: Thank you, Tian. I appreciate your wonderful insights and all your amazing contributions in the field and your research. It's really, really inspiring to see. And I'm going to transition now. Last but not least, we're having the honor of hosting professor, Dr. Tim Gilligan, who is in Cleveland Clinic, and Tim is a world-known expert in urinary cancers, including testicular cancer. Tim, would you like to introduce yourself? Dr. Gilligan: Yes. Hi. So I think you just did. Tim Gilligan, an oncologist at Cleveland Clinic. I chaired the NCCN panel on testis cancer and edit the UpToDate sections on testis cancer with their help. Dr. Grivas: Fantastic. Thanks, Tim, for being with us today. And all the work you have done for our patients with GU cancers, testicular cancer, and a lot of work is being done with the NCCN and other guidelines. And you are co-chairing the NCCN guidelines, to your point. Tim, a lot of discussion is happening nowadays across cancer types regarding the role of what we call biomarkers, which are potential features that can help us select patients for the right treatment or help us estimate the prognosis, how long people live. Could you comment a little bit on this biomarker called microRNA in patients with testis cancer? How do you envision this being developed in the future? Is it ready for prime time or not yet? Dr. Gilligan: And that's an important question. It's not ready for prime time yet, but we are making progress. There are a couple of areas where it could be very useful. So for example, in stage I testicular cancer, we tell patients to go on surveillance because they're usually cured with orchiectomy [surgical removal of the tumor and testicle], but there is a risk of relapse, and that risk of relapse is highly variable. And our current risk stratification systems for predicting who's going to relapse, who has stage 1 disease, are helpful, but they're far from perfect. And so there was data presented this year that mRNA may be more accurate at predicting for men with stage I non-seminomas who's destined to relapse. And so the implication of that would be if you are positive for mRNA, this particular mRNA for non-seminoma and you have stage I disease, normal scans, normal markers, you could identify a high-risk group of patients who maybe should get a cycle of BEP chemotherapy rather than waiting. If you know they're going to relapse, you're going to have to get them 3 cycles of BEP, why not just treat them right away? Or maybe RPLND [retroperitoneal lymph node dissection] could be helpful in that setting. We don't know. But we would need to do studies validating that approach. There is data showing that it does predict relapse, but it's not at the point of saying, "Are the patients really going to do better with immediate treatment and which treatment is going to be best for them?" But I thought that was an important finding and really an example of how we think we're going to use it, which is to find relapse a lot earlier and so that we can give a less toxic treatment. And the benefit of that is that we know more and more that chemotherapy is toxic and resulted in second cancers. For men who get multiple cycles of cisplatin-based chemotherapy, or if they get radiation therapy, they're at higher risk of dying of other cancers than the general population. So if this could help us find early relapses, treat it more gently, less aggressively, have late, less toxicity, and the same cure rate. That would be great. So we're not there yet, but I think we're going to get there. Dr. Grivas: Thanks, Tim. Very, very helpful to know. So this microRNA 371 that we talk about is not ready for prime time, but you definitely see promise for the future, and more trials, more studies are being done. Again, illustrating the importance of clinical trials that can help us evaluate the added value of a particular biomarker, including this particular microRNA that we talked about. Dr. Gilligan: Before you change the subject on getting to crude biomarkers, there was also an interesting abstract showing that for stage I seminoma. If we actually use our current markers, we may be able to predict much more accurately. And it'll be interesting to see if that changes. They looked at the variables of lymphovascular invasion, invasion of the hilum of the testis, whether or not preoperative markers were elevated, LDH, and beta HCG. What was interesting to me about that paper was that this is about 900 patients. It was pretty large. That if you had all 4 risk factors, the relapse rate was about 64%. Whereas your average relapse risk for stage I seminoma is about 15%. We put everyone on surveillance. If we started if that model is persuasive to the community and starts getting used, then maybe patients with those 4 risk markers who most of whom are going to relapse, according to this data, maybe you want to treat those people and not put them on surveillance. So that'll be interesting to follow up on too. Dr. Grivas: Thanks, Tim. And you are referring to currently available blood tests, right, that can be used, and we use them in clinical practice. So we just put them together, try to get a sense of the chance of cancer coming back, what we call recurrence, and how long people may live. That can help us make a therapy decision. Thank you, Tim. This is very, very interesting. And I'm glad to see the progress in the field. I think you alluded to that before, but there is a trend discussing when we have a removal of the testicle for a patient with testis cancer, what to do next, depending on the stage, those markers that the blood tests you told us about. What about the role of surgery for removal of lymph nodes, for example? And do you see a trend going forward that in many selective cases, certain scenarios, we may potentially select surgery as opposed to chemotherapy or radiation to avoid these potential complications down the road? And if so, which are those patients who may benefit from surgery? Dr. Gilligan: Yeah, an important question. I think surgery, there's been a growing interest in using surgery rather than chemotherapy in order to avoid late effects. So retroperitoneal lymph node dissection (RPLND) is the most obvious example of that. There is data now showing that most patients with stage II seminoma can be cured with retroperitoneal lymph node dissection. We used to treat those patients with chemotherapy or radiation, but as I've noted, both of those are associated with an increased risk of second cancers down the line. So there are papers on both sides of the Atlantic showing that you can cure most people. However, it is important to note that the relapse rate after surgery is significantly higher than the relapse rate after chemotherapy or radiation. If you take a stage II patient and treat them with chemotherapy or radiation, you're going to cure well over 90% of them. Whereas the relapse risk with surgery, depending on what you find at surgery, is going to be higher. So on average, it's going to be in the realm of 20%, maybe as high as 30%, depending on which paper you look at. And if you take patients who have PN2 disease, so a lymph node is 2 centimeters or bigger, 25% or more of those patients are relapsing after surgery. So it's important for patients to understand that this treatment has the benefit of avoiding chemotherapy for most patients, but it also has a higher risk of relapse than the old treatments. We still think it's attractive because if you can avoid chemotherapy in 3 out of 4 patients or 4 out of 5 patients, that's a benefit to those patients. And also, if you go in and find a significant amount of cancer at surgery, you can give 2 cycles of chemotherapy right away and almost eliminate the risk of relapse, which is less chemo than they would be getting upfront, which would be 3 or 4 cycles. So one of the emphasis now is really trying to avoid late toxicities if we can. You sometimes see that even in the metastatic setting in terms of resecting residual masses and situations where we maybe in the past would have thought about second-line chemotherapy. I think people are more thinking about opportunities to use surgery instead to try to limit the quantity of chemo that we're giving. Those are much trickier decisions than the stage II decisions, but definitely a growing interest in surgery rather than chemo. Dr. Grivas: Thank you so much. It's really, really exciting to see that testis cancer was really transformed in the past with developments of therapies like chemotherapy, radiation therapy, and surgery. And it's great to see this evolving down the road. And I think all of the above that you mentioned evolves through the conduction of clinical trials. And as I mentioned before, I think it's so important to give the opportunity for patients and families to review clinical trial options. I think it's critical to try to help them, but also help other patients, the community, the society in general. So I always try to underline the importance of clinical trials across the board. And on that note, I think we had such a successful year, 2023 across GU cancers. It's so great to see the progress being made. All of us are looking forward for more exciting research being done in 2024 and beyond. And on that note, I want to thank so much Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan for wonderful insights and all the great work they're doing in the field of GU cancers. As the editor for the GU Cancers for the wonderful Cancer.Net, I'm so proud of this team and really, really looking forward to further podcasts like this and how we can better serve the educational mission for ASCO, working with the wonderful staff at Cancer.Net. Thank you so much, all of you, for your time today and all you are doing. Dr. Gupta: Thank you, Petros. Dr. Zhang: Thank you, Petros. ASCO: Thank you, Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan. You can learn more about new research in genitourinary cancers at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The AUA Expert Exchange Podcast: Discussions in Managing GU Cancer: Treatment Intensification for Advanced Prostate Cancer CME Available: https://auau.auanet.org/node/39486 At the conclusion of these activities, participants will be able to: 1. Identify the latest developments in hormone therapy for advanced prostate cancer, including the use of novel treatments and combinations. 2. Discuss the concept of doublet and triplet therapy in advanced prostate cancer and its rationale in enhancing treatment efficacy. 3. Consider the challenges and future directions in implementing doublet and triplet therapy in clinical practice, including cost, accessibility, and patient selection. This series is supported by independent educational grants from: Astellas and Pfizer, Inc. AstraZeneca Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC Lantheus Medical Imaging Merck & Co., Inc. REFERENCES: Freedland SJ, et al. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023. Smith MR, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med 2022. Fizazi K, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022. Clarke NW, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022 Chi KN, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023. Agarwal N, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023.

In this "Podcast Takeover," Dr. Lidia Schapira guest hosts to discuss with Dr. Shannon Westin her own JCO paper, which reports on the DUO-E Trial. Dr. Ramez Eskander also joins in this lively discussion. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth on manuscripts published in the Journal of Clinical Oncology. I am your host, Shannon Westin, Social Media Editor of the JCO and Gynecologic Oncologist by trade. And actually, I'm super excited today because we are going to have a podcast takeover because we are discussing my own work, which was simultaneously presented at the European Society of Medical Oncology 2023 Congress and published in the Journal of Clinical Oncology on October 21st, 2023. And this was the DUO-E trial, “Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer.” Because we're discussing this work and we wanted you to have an unbiased podcast discussion, Dr. Lidia Schapira, who is a Professor of Medical Oncology at Stanford University and an Associate Editor of JCO and the Art of Oncology podcast host, is going to take over this podcast and really just pepper me with questions about this exciting work.  Welcome, Dr. Schapira.  Dr. Lidia Schapira: Thank you so much. It's such a pleasure to be with you. Dr. Shannon Westin: And before I turn over the reins, I also want to introduce one of my colleagues, who's going to be providing quite a bit of insight on this topic, Dr. Ramez Eskander, who is Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Diego. And you will know he's the principal investigator of the GY-018 study, which established pembrolizumab and chemotherapy as the new standard of care in endometrial cancer. Welcome, Ramez.  Dr. Ramez Eskander: Thank you. Thank you, Dr. Westin. It's a pleasure to be here. And congratulations again to you and your study team for this exceptional work.  Dr. Shannon Westin: Thank you. And congratulations to you.  Dr. Schapira, thank you for being here and please do take it away. Dr. Lidia Schapira: So let's start by having you tell us a little bit about the standard of care for women with endometrial cancer and advanced endometrial cancer prior to this study. Ramez, I'm going to direct this question to you first. Dr. Ramez Eskander: For many years, actually since about 2012, carboplatin and paclitaxel, which ironically is a chemotherapy backbone really across all of our gynecologic tumors, emerged as the preferred doublet chemotherapy regimen for the management of advanced-stage metastatic or recurrent endometrial cancer. It evolved through a series of different clinical trials, in fact taking us from whole abdominal radiation, systemic chemotherapy, comparing single agents to doublets and then triplet regimen of TAP to carboplatin and paclitaxel, which ultimately, then, following the presentation of GOG Protocol 209 and its publication, as the chemotherapy backbone, being carboplatin and paclitaxel. And it's been that way for many, many years. Dr. Lidia Schapira: And how effective is the regimen? Dr. Ramez Eskander: The response rates to carboplatin and paclitaxel are actually quite reasonable in the patients who have advanced-stage disease, particularly if they haven't had prior systemic chemotherapy. Response rates in the 50% to 60% range. The issue is that the responses tend to be limited and disease recurrence is an expectation in these patients who have advanced-stage disease. And so that really highlighted the importance of trying to continue to advance therapeutic opportunities in these patients to improve long-term outcomes.  Dr. Lidia Schapira: As we think about improved long-term outcomes, we're thinking about a better treatment and also a kinder treatment, perhaps one that is also less toxic. Can you talk a little bit about the population of women with endometrial cancer? Are these older women? Do they have comorbidities?  Dr. Ramez Eskander: What we're seeing is, interestingly, there has been an evolution a bit in this space. Historically, we used to think about endometrial cancer as—the phrases we used to use are type I and type II. These type I tumors, we would say, are estrogen-driven malignancies; they tend to be seen in overweight or obese patients. And we would identify them in a theoretically younger patient population. And then we had these type II, or what we termed estrogen-independent malignancies, that we would see in an older patient population. Of course, with obesity came metabolic syndrome and other cardiovascular comorbidities, etc. But really, that narrative has evolved dramatically, and that's really something that will be highlighted in, I think, our discussion of these studies today, where the nomenclature that we used to historically use has evolved because of our understanding of the molecular characterization of this disease. So we've really gone away from that, and now we understand that we're seeing all of these different heterogeneous endometrial cancer types amongst patients of different ages, different comorbidities, different races and ethnicities. And so it's created a more complex picture for us. But certainly, there are comorbidities that these patients face, and that's important as we look to identify treatments strategies that are both effective and tolerable. Dr. Lidia Schapira: My final question before we jump into this very exciting study is about the Cancer Genome Atlas work. Can you tell us how that's changed the thinking and the design of the studies? Dr. Ramez Eskander: It was a seminal publication, really, back in 2012/2013 looking at an assessment of endometrial cancers to try and determine whether or not all of these "endometrial cancers" that we used to enroll on a single study are similar or divergent. And it's important because the study I referenced that really established the standard of care, GOG Protocol 209, as carboplatin and paclitaxel, there was no real consideration of molecular characterization at all. We enrolled all patients onto this study without thinking about these variables, of course, because it was designed, conducted, and completed before the TCGA data emerged. But what we learned from the TCGA is there appeared to be four distinct molecular subgroups. There were the POLE-mutated patient population. There was the mismatch repair deficient or MSI-high endometrial cancer population. There was the copy number-high or what we say are the p53-mutated. And then the last cohort was called the NSMP (no specific molecular profile). But now, that's even evolved; some people term it TP53 wild type. That's a bit of even a heterogeneous cohort amongst itself. So we're going to take these subsets, independent of POLE and an MSI-high, and we're going to look at TP53 or copy number-high, and that will probably be divvied out further, and the NSMP, and that will probably be subdivided. But really, it gave us these four components, which has then evolved. Many of you may have heard of the ProMisE algorithm or ProMisE Plus, which looked to take the data from TCGA so that we can start to really look at it in clinical practice. So it's really revolutionized how we think about these patients, how we think about the disease, and how we design trials.    Dr. Shannon Westin: And I just want to add to that because I think that it's so important, what Ramez said about the way we were developing trials, the way we were designing trials. We knew that these classifiers—we were learning these classifiers are prognostic. Now what we're really trying to hone in on is how predictive they are. And certainly, one of the major classifiers that we're going to talking about today is mismatch repair status, and that is most definitely predictive of response to therapies. But we're still learning about the other classifiers and how we might adjust the way we treat people, even deescalating care for certain patients. That is still being proven in clinical trials, although we suspect that it's going to be borne out as other clinical trials report. Dr. Lidia Schapira: It's a perfect segue to this current trial. Tell us a little bit about the objectives and the design of DUO-E. Dr. Shannon Westin: As Ramez said, the standard of care was chemotherapy. And so we wanted to see if there was a way to improve outcomes for these women with advanced and recurrent endometrial cancer in a really clinically relevant, meaningful fashion for patients. And so we knew that this TCGA classifier, the mismatch repair, was so important, and we thought that the addition of immunotherapy to chemotherapy would most certainly work in that population but could even work in the entire population because, generally, endometrial cancer seems to be a little bit more responsive to immunotherapy and to activation of the immune system than, say, some of our other gynecologic malignancies. And so we set out to see what the addition of durvalumab, which is a PDL-1 inhibitor, would add to chemotherapy. And this was two chemo as well as followed by durvalumab maintenance.  But even further, we had some really kind of exciting science data from our lab that said that if we combined a PARP inhibitor with immunotherapy that we could accentuate on the response to therapy and we could get more benefit. And there's kind of a lot behind that, but essentially, what we thought was that the damage that's caused by the PARP inhibitors would create an activation of different immuno-pathways, like STING pathway and activating cytokine release, and that we would get this synergistic activity. So one of the other objectives was to see if the addition of the olaparib, the PARP inhibitor, to durvalumab in that maintenance setting could even further improve benefit. So we had a dual primary endpoint looking at progression-free survival, so the amount of time people live without their cancer coming back. And that endpoint was first, the durvalumab-alone arm to control, and then the second portion of that was the durvalumab/olaparib arm back to control. Dr. Lidia Schapira: So before you tell us about the results, tell us a little bit about the study itself. I mean, I was very impressed that you did it in so many different locations. Tell us about that effort.  Dr. Shannon Westin: This was a huge collaborative effort both with the GOG Foundation, the Gynecologic Oncology Group Foundation, as well as ENGOT, which is our European colleagues that do amazing clinical trials. But in addition to that, we really worked very closely with our industry partner to really make sure we spanned the globe. And so we had groups from all over the world that participated and really were exceptional. The care that was taken and the hard work that went into this type of study across the world really can't be overstated. We were very lucky to have a wonderful infrastructure group. We met weekly for a long time, just keeping an eye on the data and making sure that everything was as positive as possible and, of course, that we were watching the outcomes of the patients very closely and making sure that there was no evidence of harm or issue. And so it really did take a village, truly, to run this study and to ensure that at the end of it, we got really great data that we can trust. Dr. Lidia Schapira: So tell us the results. Dr. Shannon Westin: So DUO-E was positive for both of its primary endpoints, which was very thrilling. So for the first analysis, which is the durva-alone arm to control, we saw a reduction in the risk of progression of 29%, so a hazard ratio of 0.71. And then the addition of olaparib seemed to further enhance this benefit, so a 45% reduction in the risk of progression for a hazard ratio of 0.55. But what's really exciting is our follow-up time was pretty long; it was about 17 months, so we were able to look at a couple of different analyses, including an 18-month landmark analysis where we saw approximately 50% of the patients were still alive progression free at 18 months, as compared to only 21% of patients being alive progression free in the control arm. So there was a doubling in that progression-free survival time point at 18 months, which is thrilling. Dr. Lidia Schapira: So Ramez, as an expert in the field, what was your reaction when you read or heard these results?  Dr. Ramez Eskander: It's exciting, honestly. So we have gone a long time without seeing really significant successes in the endometrial cancer space, a testament to the fact that we hadn't yet developed our understanding of how we could move this needle forward. But Dr. Westin and the DUO-E team conducted an exceptional clinical trial, as you mentioned, international study, rational and important hypothesis to adjudicate. And what we saw here was both now we had other studies—the RUBY trial, the GY018 trial, the  AtTEnd—and now here DUO-E, which added this hypothesis of PARP maintenance in addition to checkpoint to try to augment response and consistent, really provocative data, exciting, in line with what we've seen and hopefully will continue to drive the science in this space, most importantly. Dr. Lidia Schapira: So let me ask you a follow-up question to that. What kind of scientific questions are in the air now as a result of this trial and what the trial found? Dr. Ramez Eskander: Oh, goodness. Shannon and I could both take this, I'm sure. But I think in the dMMR population, we recognize that there's a ton of data that is supportive of the fact that these tumors are immune responsive, particularly in dMMR endometrial cancer, whether it's an epigenetic promoter hypermethylation, or a mismatch repair gene mutation. I think the data has emerged that immunotherapy is here to stay for these patients in the newly diagnosed advanced stage, even chemo naïve, who need adjuvant therapy.   The pMMR population, this is where we're seeing more and more questions emerge because we realize that that may be a cohort of different cancers. And I'll let Shannon speak to this briefly, but even the incorporation of the PARP inhibitor, in addition to the checkpoint, there's a biologic rationale for combining those two together to augment response. And to see the benefit in that trial—arm three and arm two, we can look at descriptively and look at the differences, but who are those patients? Where is the PARP and the checkpoint most effective? How do we expand that to a larger population of patients potentially? These are questions that emerged because, as Dr. Weston will allude to, I know we also talk about HRR mutations, which are captured, but we even have a lot to understand about that in endometrial cancer, where we've had more research in the ovarian cancer space. Dr. Shannon Westin: Being mindful of time, because I have, like, 1,000 hypotheses that have been generated by this study, which, I think, shows it's a great study, right? Because you get some answers, and as our colleague Brad Monk says, “The only definitive study is the negative studies.” This most certainly was not that. But just kind of expanding on what Ramez said, the interesting thing about DUO-E is that really the biggest benefit for the combination of the durvalumab and olaparib was in that mismatch repair proficient group. And I personally thought that we were going to see accentuation of the impact in the mismatch repair deficient group based on the science, but that just wasn't borne out by the data. It doesn't seem that the combination has that much to add in that mismatch repair deficient group. And when we tease out the mismatch repair proficient group, I think that's where a lot of interesting information is going to come because, to Ramez's point, we're going to tease out: Is it driven by the P53-mutant population? Is it driven by the population that has homologous recombination deficiency? How do we even measure homologous recombination deficiency in endometrial cancer? So I'm super excited about what we found and how that may help us to make those decisions for the patient in front of us.  The other thing I think needs to be made mention of—and this was something we saw in DUO-E as well as AtTEnd—we had a large population of patients that were recruited in Asia, 30%. Interestingly, when we look at the forest plot, that group doesn't seem to benefit as much from the addition of the olaparib. So we really need to tease out what's different about that population because what Nicoletta Colombo presented around AtTEnd, it looked like they didn't benefit from the atezolizumab either in that study. So there's clearly something different about that population, and we have a really big opportunity to look at that since we had such a large proportion of patients that were enrolled there. So that's another, I think, really intriguing question. Dr. Lidia Schapira: So how does this fit in the context of endometrial cancer treatment, and what are we going to do with patients in the clinic? I'd love to hear both of your perspectives, starting with you, Ramez. Dr. Ramez Eskander: It's an evolving answer, to say the least. What we can say definitively is that we have a United States FDA approval for the regimen of dostarlimab plus carboplatin and paclitaxel in the mismatch repair deficient, advanced-stage/recurrent or metastatic patient cohort. And again, that's because the magnitude of benefit that we saw in the RUBY trial, which looked at that, was actually analogous to what we saw in 018, AtTEnd, and DUO-E, again, consistently highlighting the benefit of the IO and the dMMR. We have yet to see how this is going to evolve the landscape in the larger patient population, which is the pMMR patient population. And it may be that based on the data that we have, we will see immunotherapy plus carboplatin and paclitaxel as the new standard of care in the pMMR cohort, or it may not. That's yet to be defined. And I think Dr. Westin will add to this, but I think that's also going to depend on the perception of how we view the cohort. Is it one group of patients? Are we going to have to think about subsets within the pMMR population? That is an active conversation. Dr. Shannon Westin: I would just add, having treated patients on this combo regimen with the durvalumab and olaparib, I have multiple patients that still remain on study, and this—we're looking at three and four years out. I just never saw anything like that before with standard chemotherapy, so there's definitely something here. So I want to know who those patients are, who benefits really the best from the combination, and who could we just give the immunotherapy to and get that same benefit. So we obviously always want people to live as long as possible. That's the bottom line. But we don't want to overtreat. And so I think balancing that is really important. Dr. Ramez Eskander: The point that was made earlier: We have yet, aside from MMR response to checkpoint, within the pMMR population, we understand that there may be subsets, but we have yet to prospectively validate that these molecular cohorts within the pMMR population are truly defining response to a particular therapeutic strategy. So we have to be cautious not to limit the treatment opportunities for these patients without having the data that we need to do so because, as Dr. Westin mentioned, for us—whether it was the Gy018 trial, the RUBY, the DUO-E trial—what we saw is there are pMMR patients who have a dramatic response even though they are “biomarker negative.” They're pMMR, they're TMB low, they're not POLE mutated, but yet they still derive a dramatic benefit. And so that goes back to the hypothesis about why we're even combining checkpoint with chemotherapy in which, for example, in lung cancer, there's been established success and approval. So I think we're all eager to see these strategies emerge as treatment opportunities for the pMMR patients as we work to still develop additional effective opportunities. Dr. Lidia Schapira: So, based on all of this and sort of the new twists on the scientific hypotheses that are now generated, what are the next steps? Dr. Shannon Westin: Well, I think we have to see if these drugs are available for patients. So looking at things like compendium listing and regulatory approvals obviously is going to be very important. But from the things that I can control, we are looking at the different molecular subtypes and understanding the different mutation status and trying to tease out who may be driving the biggest benefits so that we can help advise and make sure that we're doing the right thing for the patients. Dr. Lidia Schapira: And wearing my supportive care hat, I have to ask you, Shannon, about the tolerability. We often find that the quality of life and studies come out after, sometimes months or years after, the original trials are published. So let me take this opportunity to ask you now: How did women tolerate these drugs? Dr. Shannon Westin: The bottom line, Lidia, is, as expected, when you add additional drugs, you see additional side-effects. I think the good thing is that we're very comfortable with immunotherapy and we're very comfortable with PARP inhibition in gynecology because we have had access to these agents and so we know how to manage the toxicities. And so, from a standpoint of incidence, there was a higher incidence of grade three and higher adverse events in the group that had durvalumab/olaparib. But this was primarily driven by anemia, which is as expected and is usually pretty time-limited at the start of olaparib. From a long-term standpoint, there was a slightly higher proportion of patients that discontinued therapy, but it actually wasn't as much as I was worried about. So we saw a 19% discontinuation rate in the group that was just the control arm, and that went up to 24% in the dual arm, so definitely higher, but not that much higher. And when we moved to maintenance, which is really where—that's where the arm becomes unique, it was much lower at about 12%. And so that's exciting to me, that patients were able to stay on a drug and were able to tolerate it.  And then, to your other point, we do have a very nice patient-reported outcomes plan, and that is actually being analyzed as we speak with the hope of presenting it at the next major meeting, our Society of GYN Oncology meeting in March. So not right away, but I think in a pretty timely fashion, we'll have those data. Dr. Lidia Schapira: Congratulations, Shannon, on leading and presenting this wonderful study. So it's been a real pleasure to chat with the two of you. Dr. Ramez Eskander: Thank you. Dr. Shannon Westin: Thanks so much, Lidia. I really appreciate it. Thanks, Ramez, for being here.  And I will just say thank you to all of our listeners. We really hope you enjoyed this episode of JCO After Hours, where we discussed the DUO-E trial, which is a phase III trial evaluating durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer. And again, please do enjoy this publication that was online at the Journal of Clinical Oncology on October 21st, 2023. And do check out our other podcast offerings wherever you get your podcasts. Have a wonderful day. 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.      

Join Drs Kevin Kalinsky and Jennifer Litton as they discuss hereditary breast cancer, genetic testing, and therapeutic implications. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991258). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources A Review of Triple-negative Breast Cancer https://www.medscape.com/viewarticle/727195_4 PARP and PARG Inhibitors in Cancer Treatment https://pubmed.ncbi.nlm.nih.gov/32029455/ BRCA1 and BRCA2 Mutations https://www.ncbi.nlm.nih.gov/books/NBK470239/ Iniparib Plus Chemotherapy in Metastatic Triple-negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/21208101/ Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant https://pubmed.ncbi.nlm.nih.gov/31461380/ ER/PgR Testing in Breast Cancer Clinical Practice Guidelines (ASCO/CAP, 2020) https://reference.medscape.com/viewarticle/924542 Pathological Complete Response in Neoadjuvant Treatment of High-risk Early-stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval Guidance for Industry https://www.fda.gov/media/83507/download Adjuvant Olaparib for Patients With BRCA1- or BRCA2-mutated Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34081848/ PALB2 Partner and Localizer of BRCA2 https://www.ncbi.nlm.nih.gov/gene/79728 Pre-specified Event Driven Analysis of Overall Survival (OS) in the OlympiA Phase III Trial of Adjuvant Olaparib (OL) in Germline BRCA1/2 Mutation (gBRCAm) Associated Breast Cancer https://oncologypro.esmo.org/meeting-resources/esmo-virtual-plenary-resources/olympia-phase-iii-pre-specified-event-driven-analysis-of-overall-survival-of-olaparib-in-gbrcam-breast-cancer Pembrolizumab for Early Triple-negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/32101663/ Olaparib for Metastatic Breast Cancer in Patients With a Germline BRCA Mutation https://pubmed.ncbi.nlm.nih.gov/28578601/ Talazoparib in Patients With Advanced Breast Cancer and a Germline BRCA Mutation https://pubmed.ncbi.nlm.nih.gov/30110579/ Veliparib With Temozolomide or Carboplatin/Paclitaxel Versus Placebo With Carboplatin/Paclitaxel in Patients With BRCA1/2 Locally Recurrent/Metastatic Breast Cancer: Randomized Phase II Study https://pubmed.ncbi.nlm.nih.gov/29045554/ RAD51 Recombinase https://www.ncbi.nlm.nih.gov/gene/5888 The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice https://pubmed.ncbi.nlm.nih.gov/34068084/ Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq Tissue-agnostic Drug Approvals: How Does This Apply to Patients With Breast Cancer? https://pubmed.ncbi.nlm.nih.gov/34518552/

Drs Sandhya Srinivas and Heather Cheng discuss PARP inhibitors, clinical trials, and germline vs somatic testing for patients with prostate cancer, as well as the optimal time for this testing. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988734). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Germline Testing in Prostate Cancer: When and Who to Test https://pubmed.ncbi.nlm.nih.gov/34669358/ Germline and Somatic Mutations in Prostate Cancer for the Clinician https://pubmed.ncbi.nlm.nih.gov/31085765/ Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair https://pubmed.ncbi.nlm.nih.gov/37207301/ Genome-Wide Association Study of Prostate Cancer-Specific Survival https://pubmed.ncbi.nlm.nih.gov/26307654/ Inherited DNA-Repair Gene Mutations in Men With Metastatic Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/27433846/ NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf PARP Inhibitors in Metastatic Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/37168382/ Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration https://pubmed.ncbi.nlm.nih.gov/32795228/ Olaparib for Metastatic Castration-Resistant Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/32343890/ Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200043 Rucaparib or Physician's Choice in Metastatic Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/36795891/ FDA Approves Olaparib With Abiraterone and Prednisone (or Prednisolone) for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/36952634/ Talazoparib Plus Enzalutamide in Men With First-line Metastatic Castration-Resistant Prostate Cancer (TALAPRO-2): A Randomised, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/37285865/

Listen to a soundcast of the May 31, 2023, FDA approval of Lynparza (olaparib), with abiraterone and prednisone, for BRCA-mutated metastatic castration-resistant prostate cancer.”

In this episode, Sarah Hayward, PharmD, BCOP, and Amy Ly Indorf, PharmD, BCOP, discuss their experiences providing care for patients with advanced ovarian cancer, with topics including:PARP inhibitors as frontline maintenance therapyPatient education and counseling on PARP inhibitorsHelping patients access newer therapiesExperiences with mirvetuximab soravtansinePatient education and counseling on mirvetuximab soravtansineTreatment modalities on the horizon Presenters:Sarah Hayward, PharmD, BCOPClinical Pharmacy Specialist,Gynecologic OncologyStephenson Cancer Center atOU HealthOklahoma City, OklahomaAmy Ly Indorf, PharmD, BCOPClinical Assistant ProfessorUniversity of Washington School of PharmacyClinical Oncology PharmacistUW MedicineFred Hutchinson Cancer CenterSeattle, WashingtonSupported by educational grants from GSK and Novocure, Inc.Link to full program:https://bit.ly/44fUiOU 

Featuring perspectives from Dr Komal Jhaveri, Dr Kevin Kalinsky, Dr Ian E Krop, Dr Joyce O'Shaughnessy, Dr Hope S Rugo and Prof Peter Schmid, including the following topics: Long-Term Management of HER2-Positive Breast Cancer Introduction (0:00) Management of CNS-only disease progression in patients with HER2-positive metastatic breast cancer (2:27) Synergy between tucatinib and HER2-targeted antibody-drug conjugates (5:24) Management of trastuzumab deruxtecan–related adverse events (7:41) Patient selection for and practical implementation of postadjuvant neratinib (13:23) Faculty presentation: Dr Krop (16:26) Optimizing the Management of ER-Positive Localized Breast Cancer Ovarian function suppression to preserve fertility and prevent premature ovarian insufficiency; interrupting adjuvant hormonal therapy to attempt pregnancy (24:56) Selection of patients for adjuvant tamoxifen monotherapy (29:05) Utility of genomic assays in the neoadjuvant setting; management of node-positive disease in postmenopausal patients with low-risk Recurrence Scores® (33:35) Selection between abemaciclib and ribociclib in the adjuvant setting (36:45) Potential utility of circulating tumor DNA assessment in breast cancer (41:58) Faculty presentation: Dr Kalinsky (46:36) Considerations in the Care of Patients with ER-Positive Metastatic Breast Cancer Preference of CDK4/6 inhibitor in the metastatic setting (56:42) Sequencing of trastuzumab deruxtecan in ER-positive, HER2-low metastatic breast cancer (59:00) Faculty presentation: Dr Jhaveri (1:06:39) Novel and Emerging Strategies for ER-Positive Metastatic Breast Cancer Selection of therapy for ER-positive metastatic breast cancer progressing on a CDK4/6 inhibitor; future role of capivasertib (1:19:31) Faculty presentation: Dr Rugo (1:30:39) Evolving Clinical Decision-Making for Localized Triple-Negative Breast Cancer (TNBC) Management of localized TNBC; selection of patients for adjuvant Olaparib (1:46:10) PARP inhibitor tolerability (1:51:55) Faculty presentation: Dr O'Shaughnessy (1:55:31) Recent Advances in the Treatment of Metastatic TNBC (mTNBC) Selection of therapy for triple-negative metastatic breast cancer; sequencing of trastuzumab deruxtecan in ER-negative, HER2-low disease (2:11:08) Faculty presentation: Prof Schmid (2:18:03) CME information and select publications

Dr Armstrong discusses the FDA approval of olaparib plus abiraterone in patients with BRCA-mutated mCRPC, key efficacy and safety data from the PROpel trial, and where the field of prostate cancer research may be headed in the future.

Olaparib + Abiraterone is FDA approved for mutated-BRCA prostate cancers. Olaparib has a bit of convoluted story to unpack in this patient population. Have we finally found a way to minimize the peripheral neuropathy from paclitaxel.....with cilostazol? PROpel: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200043 Cilostazol RCT: https://doi.org/10.1002/phar.2830 Cilostazol effect on Schwann cells: https://doi.org/10.1016/j.neuropharm.2021.108514

Just imagine it is 2 AM and you need to learn about a drug, but you don't have a lot of resources. What can you grab quickly? This episode's guest has the perfect book for you. Nicole Kupchik, MN, RN, CCNS, CCRN-CMC, PCCN-K has written Critical Care Survival Guide, a concise bedside reference book for anyone working in critical care regardless of experience level. In today's conversation, Nicole joins Jenny Finnell to give us access to some of the wisdom from her book, particularly on ICU cardiac medications. They break down the five cardiac medications we commonly see—norepinephrine, epinephrine, Olaparib, milrinone, and dobutamine—and discuss how to titrate them. Tune in to learn more about these cardiac medications, adding more to your CRNA information toolkit! Get access to planning tools, mock interviews, valuable CRNA Faculty guidance, and mapped-out courses that have been proven to accelerate your CRNA success! Become a member of CRNA School Prep Academy here! https://www.crnaschoolprepacademy.com/join Book a mock interview, personal statement, resume and more at http://www.NursesTeachNurses.com Join the CSPA email list here! https://www.cspaedu.com/podcast-email Send Jenny an email or make a podcast request! Hello@CRNASchoolPrepAcademy.com Grab Nicole Critical Care Survival Guide: https://www.nicolekupchikconsulting.com/booksAndCourses/books-bundles/136/critical-care-survival-guide USE COUPON CODE: FUTURECRNA20 for 20% off!

Jorge Garcia discusses the recent ODAC meeting for the FDA.

In this episode, Banu Arun, MD; Allison Butts, PharmD, BCOP; and Marissa Marti-Smith, MSN, APRN, AGNP-C, AOCNP, discuss the role of BRCA testing and adjuvant olaparib in early breast cancer, including their experiences and challenges with implementing recent data. This overview will include discussion of:  Data supporting the use of adjuvant PARP inhibition in early breast cancer and impact on BRCA testing and clinical practice The multidisciplinary role in ensuring that BRCA testing is completed for eligible patients Barriers to implementing BRCA testing and adjuvant olaparib in clinical practice and methods to overcome them Administration of adjuvant olaparib with other available adjuvant systemic therapiesTolerability of single-agent PARP inhibitors  Presenters:Banu Arun, MDProfessor, Breast Medical Oncology Director, Clinical Cancer Genetics University of Texas MD Anderson Cancer Center Houston, Texas  Allison Butts, PharmD, BCOPPharmacist Manager, Oncology Director, PGY2 Oncology Residency Program UK HealthCare Assistant Adjunct ProfessorUK College of Pharmacy Lexington, Kentucky Marissa Marti-Smith, MSN, APRN, AGNP-C, AOCNPNurse Practitioner Breast OncologyTexas Oncology Baylor Sammons Cancer Center Dallas, Texas  Content supported by educational grants from AstraZeneca and Merck Sharp & Dohme Corp. Link to full program:https://bit.ly/42VeUMM

In this podcast episode from a live CCO Cancer Conversations webinar, Mark Pegram, MD, and Sara Tolaney, MD, MPH, provide expert perspectives on optimal treatment strategies for patients with triple-negative breast cancer (TNBC), with topics including:Current data and strategies for using PD-1/PD-L1 inhibitors in early-stage TNBC Clinical implications of PD-L1 status on therapeutic planning for patients with metastatic TNBC Current data and treatment strategies and the future of antibody–drug conjugates in the management of relapsed/refractory advanced TNBC Treatment implications of the presence of BRCA1/2 mutations and homologous recombination deficiency genes in advanced TNBCRole of PARP inhibitors in the treatment of TNBCPresenters: Mark Pegram, MDProfessor Medical OncologyStanford UniversityPalo Alto, CaliforniaSara Tolaney, MD, MPHAssociate Professor of MedicineDivision of Breast OncologyHarvard Medical SchoolChief, Division of Breast OncologyBreast Oncology ProgramDana-Farber Cancer InstituteBoston, MassachusettsContent based on an online CME/CE/CPE program supported by educational grants from Gilead Sciences, Inc.Link to full program:http://bit.ly/3iQzDz5

Dan George and Silke Gillessen disagree amicably. 

In dieser Folge geht es um die „PROPEL-Studie“, die eine Kombinationstherapie mit Abirateron und dem PARP-Inhibitor Olaparib in der ersten Behandlungslinie des mCRPC untersucht. Gunhild von Amsberg und Markus Graefen erläutern im Podcast das Phänomen der medikamentös ausgelösten „BRCAness“ und betrachten die Ergebnisse anderer Studien zur Kombination aus PARP-Inhibitor und Androgenrezeptor-gerichtetem Medikament.

In this episode,Susana Banerjee, MBBS, MA, PhD, and Mansoor Raza Mirza, MD, share their thoughts on key studies of interested presented at the IGCS 2022 Annual Global Meeting for ovarian and cervical cancers including:Post-hoc analyses from SOLO-3: olaparib vs physician's choice chemotherapy in germline BRCA mutant platinum-sensitive recurrent ovarian cancerPhase III CALLA trial: durvalumab combined with and following chemoradiation for locally-advanced cervical cancerPhase III ARIEL3: final OS for maintenance rucaparib vs placebo following response to platinum-based chemotherapy for recurrent high-grade serous ovarian cancerRetrospective NeCTuR study: outcomes with topotecan, paclitaxel, and bevacizumab (TPB) vs non-TPB regimens for recurrent high-grade neuroendocrine carcinoma of the cervixPresenters:Susana Banerjee, MBBS, MA, PhD, FRCPConsultant Medical Oncologist and Research LeadGynaecology UnitRoyal Marsden NHS Foundation TrustLondon, United KingdomMansoor Raza Mirza, MDChief OncologistDepartment of OncologyRigshopitalet – Copenhagen University HospitalCopenhagen, DenmarkContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/38xuRBv

In this episode, Domenica Lorusso, MD, PhD, and Alexandra Leary, MD, PhD, provide their expert insights on key updates presented for ovarian cancer trials including:Phase III GOG-3004/SOLO-1: OS results after 7 years of follow-up for patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib vs placeboPhase III ENGOT-ov25/PAOLA-1: final OS results from the trial of maintenance therapy with olaparib with bevacizumab vs bevacizumab alone in women with newly diagnosed advanced ovarian cancerPhase III ATHENA-MONO: outcomes by disease subgroups receiving rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancerPhase III ARIEL4: OS outcomes following treatment with rucaparib vs chemotherapy in patients with relapsed advanced ovarian cancer and a deleterious BRCA1/2 mutationPresenters:Domenica Lorusso, MD, PhDAssociate ProfessorGynecologic Oncology DepartmentClinical Research UnitFondazione Policlinico Gemelli IRCCSRome, ItalyAlexandra Leary, MD, PhDMedical Oncologist and Team LeaderGynecology Translational Research LabDepartment of MedicineGustave Roussy Cancer CenterParis, FranceContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries: https://bit.ly/3SSSqpN

Novavax vaccine booster update; over-the-counter hearing aids; priority review for a castration-resistant prostate cancer combination treatment; a first gene therapy approved for beta-thalassemia; FDA urges repeat at home COVID-19 testing to reduce risk of missing infection.

In this episode, Brenda Martone, MSN, ANP-BC, AOCNP describes recent evidence on PARP inhibitor therapy in metastatic castrate-resistant prostate cancer (mCRPC) and discusses best practices for incorporating PARP inhibitors into clinical practice. Topics include:An overview of the PROpel study of olaparib and the TRITON study of rucaparibFDA-approved indications for olaparib and rucaparibGenetic and molecular testing for BRCA1/2 and other HRR mutationsManaging adverse events associated with olaparib and rucaparibMonitoring for and managing anemiaGastrointestinal side effectsFatigueA look at the future of PARP inhibitors in mCRPC with combination approaches of AR-directed therapy and PARP inhibitionPresenter:Brenda Martone, MSN, ANP-BC, AOCNPNurse PractitionerDivision of Genitourinary OncologyNorthwestern MedicineChicago, IllinoisLink to full program:PCE.is/Onc22

The cancer risks that run through generations of families—and the growing frontier in medicine trying to change that.

This episode is sponsored by the Osteosarcoma Institute (OSI), a nonprofit organization led by osteosarcoma experts from top U.S. cancer centers who, together, are concentrating on the cure for osteosarcoma. The mission of the OSI is to dramatically increase treatment options and survival rates in osteosarcoma patients through identifying and funding the most promising and breakthrough osteosarcoma clinical trials and science. In addition to advancing research, OSI also provides a free resource called OSI Connect for osteosarcoma patients. Our osteosarcoma experts can discuss available treatments, possible side effects, and provide helpful advice for getting the most out of your visits with your treating physician. This resource is available in English and Spanish and aims to help patients and families find answers to their questions. What We Do at MIB Agents: PROGRAMS: ✨ End-of-Life MISSIONS ✨ Gamer Agents ✨ Agent Writers ✨ Prayer Agents ✨ Healing Hearts - Bereaved Parent Support ✨ Ambassador Agents - Peer Support ✨ Warrior Mail ✨ Young Adult Survivorship Support Group ✨ EDUCATION for physicians, researchers and families: ✨ OsteoBites, weekly webinar & podcast with thought leaders and innovators in Osteosarcoma ✨ MIB Book: Osteosarcoma: From our Families to Yours ✨ RESEARCH: Annual MIB FACTOR Research Conference ✨ Funding $100,000 annually for OS research ✨ MIB Testing & Research Directory ✨ The Osteosarcoma Project partner with Broad Institute of MIT and Harvard ... Kids are still dying with 40+ year old treatments. Help us MakeItBetter.

Featuring an interview with Dr Judy Garber, including the following topics: Applying the FDA indications for PARP inhibitors in breast cancer (0:00) Role of HRD (homologous recombination deficiency) and loss of heterozygosity in assessing patient risk; potential role for PARP inhibitors and other therapies for patients with mutations in genes other than BRCA1/2 (7:04) Efficacy data from the NEOTALA and OlympiA trials (11:30) Case: A woman in her late 30s newly diagnosed with invasive ductal breast carcinoma (16:55) Considerations for genomic testing for patients with breast cancer (22:46) Impact of COVID-19 on genetic counseling; PARP inhibitors as prevention; major toxicities with olaparib (27:28) Case: A woman in her early 50s with residual disease after neoadjuvant therapy for triple-negative breast cancer (33:59) Case: A woman in her mid 30s with metastatic disease who experiences disease progression on palbociclib and Olaparib (35:33) Future roles of PARP inhibitors in the management of breast cancer; impact of iniparib on PARP inhibitor research (38:57) CME information and select publications

Drs Lidia Schapira and Nadine Tung discuss how BRCA status affects choosing therapy for patients with early-stage breast cancer. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/963168). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462533/ Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer https://www.nejm.org/doi/full/10.1056/NEJMoa2105215 Validation of a Novel Staging System for Disease-Specific Survival in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107758/ Table 1 from Validation of a Novel Staging System for Disease-Specific Survival in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107758/table/T1/?report=objectonly Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339/ Evaluation of Efficacy and Safety of PARP Inhibitors in Breast Cancer: A Systematic Review and Meta-analysis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215282/pdf/main.pdf LYNPARZA® (olaparib) Prescribing Information. AstraZeneca; 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline https://ascopubs.org/doi/full/10.1200/JCO.20.00299 A Population-Based Study of Genes Previously Implicated in Breast Cancer https://www.nejm.org/doi/full/10.1056/NEJMoa2005936 TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes https://ascopubs.org/doi/10.1200/JCO.20.02151 Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers https://academic.oup.com/jnci/article/97/11/813/2521263?login=false Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 (gBRCA1/2) Mutation-Positive, Early HER2-Negative Breast Cancer (BC): Results of a Phase 2 Study https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.505

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

In this episode, Eileen M. O'Reilly, MD, and Naureen Starling, MD, FRCP,  discuss emerging therapeutic strategies involving PARP inhibitor therapy in the treatment of pancreatic cancer. Topics include:Current treatment landscape and testing in the United States vs the United Kingdom  Testing for molecular subgroups beyond BRCAmUsing PARP inhibitors in earlier stages of the diseaseLearning from other cancers, such as prostate, breast, and ovarian  Presenters:Eileen M. O'Reilly, MDWinthrop Rockefeller Chair in Medical OncologySection Head, Hepatopancreaticobiliary/Neuroendocrine CancersGastrointestinal Oncology ServiceAssociate DirectorDavid M. Rubenstein Center for Pancreatic CancerAttending Physician, MemberMemorial Sloan Kettering Cancer CenterProfessor of MedicineWeill Medical CollegeNew York, New York, USANaureen Starling, MD, FRCPAssociate Director of Clinical ResearchDepartment of GI CancersConsultant Medical Oncologist, GI CancersThe Royal Marsden HospitalLondon, United KingdomContent based on an online CME program supported by an educational grant from AstraZeneca.Link to full program:https://bit.ly/3s6AnSz

Fred Saad describes the results of this trial. 

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

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

In this episode, Nicoletta Colombo, MD; Philipp Harter, MD, PhD; and  Alexandra Leary, MD, PhD, discuss patient cases from a live webinar on the current paradigm and long-term benefits of PARPi therapy in the treatment of ovarian cancer. Topics include:Maintenance therapy in ovarian cancerSOLO1, PRIMA, PAOLO-1 clinical dataRole of bevacizumab in treatment of ovarian cancerPresenters:Nicoletta Colombo, MDProfessor of Obstetrics and GynecologyUniversity of Milan-BicoccaEuropean Institute of OncologyMilan, ItalyPhilipp Harter, MD, PhDDeputy DirectorDepartment of Gynecology and Gynecologic OncologyEvang. Kliniken Essen-MitteEssen, GermanyAlexandra Leary, MD, PhDMedical Oncologist and Team LeaderGynecology Translational Research LabDepartment of MedicineGustave Roussy Cancer CenterParis, FranceContent based on an online CME program supported by an educational grant from AstraZeneca.New Perspectives in Ovarian Cancer: Current Paradigm and Long-term Benefits of PARPi Therapyhttps://bit.ly/3aF8Lui 

In this episode, John L. Marshall, MD, discusses current molecular testing considerations in the treatment of patients with gastrointestinal tumors, including:Current testing approaches, including IHC and PD-L1 assays and next-generation sequencingTumor agnostic testing: MSI, TMB, and NTRK fusion testingColon cancer: RAS, BRAF, and HER2Gastric cancer: PD-L1, HER2, and morePancreatic cancer: BRCABiliary cancers: FGFR and IDH1Liquid biopsiesWhen to testPresenter:John L. Marshall, MDChief, Division of Hematology/OncologyDepartment of MedicineGeorgetown University HospitalWashington, DCContent based on an online CME program supported by educational grants from Bayer and Merck, Sharp & Dohme.Link to full program:https://bit.ly/3j4hV8J

In this episode, Linda R. Duska, MD, MPH; Robert L. Coleman, MD, FACOG, FACS; and Leslie Randall, MD, MAS, answer questions from an audience of healthcare professionals on topics related to the management of patients with endometrial and ovarian cancer including:  Adding bevacizumab to chemotherapy in frontline endometrial cancerLenvatinib and pembrolizumab in MSI-H/dMMR endometrial cancerPARP inhibitor maintenance in ovarian cancerBevacizumab with or without PARP inhibitors in ovarian cancerPresenters:Linda R. Duska, MD, MPHLawrence W. Penniston MD Family Professor in Women's Oncology ResearchDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyUniversity of Virginia School of MedicineCharlottesville, VirginiaRobert L. Coleman, MD, FACOG, FACSGynecologic Oncologist and Chief Scientific OfficerUS Oncology, US Oncology ResearchThe Woodlands, TexasLeslie Randall, MD, MAS  Diane Harris Wright Professor and DirectorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyMassey Cancer CenterVirginia Commonwealth UniversityRichmond, VirginiaLink to full program, including downloadable slidesets, expert commentaries, and on-demand webcast:https://bit.ly/3e6pZCM 

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

El Dr. Yair Baas Cabrera, oncólogo médico adscrito al Hospital Regional 1, IMSS en Mérida (Yucatán, México), comenta en este video sobre lo más destacado en sarcomas presentado en ASCO 2021, resaltando los siguientes estudios: SPEARHEAD: Estudio fase II, de células T ADP-A2M4 SPEAR en pacientes con sarcoma sinovial avanzado o liposarcoma mixoide de células redondas. APROMISS: Estudio fase lll, que evalúa la seguridad y eficacia del hidrocloruro de AL3818 en el tratamiento del sarcoma de partes blandas alveolar avanzado metastásico o avanzado, leiomiosarcoma y sarcoma sinovial. Olaparib + temozolamida: Estudio fase ll, que estudia esta combinación en el tratamiento de pacientes con leiomiosarcoma uterino diseminado a otras partes del cuerpo (avanzado/metastásico) o que no se puede extirpar mediante cirugía. PEMBROSARC: Estudio fase ll, combinación de MK3475 y ciclofosfamida metronómica en pacientes con sarcomas avanzados. SEAL: Estudio fase lll, evaluó selinexor oral como agente único vs. placebo equivalente en pacientes con liposarcoma desdiferenciado irresecable avanzado alcanzó su criterio de valoración principal de un aumento estadísticamente significativo en la supervivencia libre de progresión.

Recent approvals of PARP inhibitors mark the beginning of precision medicine for prostate cancer. Through patient case scenarios, Drs. Lisa Holle (Oncology Pharmacist, University of Connecticut) and Pedro C. Barata (Medical Oncologist, Tulane University) dive in-depth into appropriate use of olaparib and rucaparib in clinical practice, including patient and disease factors to consider. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us

In this episode, Karim Fizazi, MD, PhD, and Joaquin Mateo, MD, PhD, consider the potential implications of ongoing and planned clinical trials using PARP inhibitors in combination with other therapies to treat men with prostate cancer including:PARP inhibitors combined with androgen receptorsPhase III trials of PARP inhibitors with androgen receptor–directed therapyPARP inhibitors combined with immunotherapyPARP inhibitors and DNA damaging agentsPresenters:Karim Fizazi, MD, PhDFull ProfessorCancer MedicineInstitut Gustave RousseyVillejuif, FranceJoaquin Mateo, MD, PhDAttending PhysicianMedical OncologyVall d’Hebron University Hospital,Barcelona, SpainContent is part of an online program supported by an educational grant from Pfizer Inc.Link to full program, including associated downloadable Podcast Pearls slidesets, expert analysis, and expert commentary:https://bit.ly/3spLzqa

In this episode, Karim Fizazi, MD, PhD, and Joaquin Mateo, MD, PhD, discuss the underlying rationale for using PARP inhibitors in combination with other therapies to treat men with prostate cancer including:Possible synergy between PARP inhibitors and androgen receptor–directed therapyRationale for PARP inhibitors and immunotherapy combinationsBenefits and challenges of combining DNA damaging agents and PARP inhibitorPresenters:Karim Fizazi, MD, PhDFull ProfessorCancer MedicineInstitut Gustave RousseyVillejuif, FranceJoaquin Mateo, MD, PhDAttending PhysicianMedical OncologyVall d’Hebron University Hospital,Barcelona, SpainContent is part of an online program supported by an educational grant from Pfizer Inc.Link to full program, including associated downloadable Podcast Pearls slidesets, expert analysis, and expert commentary:https://bit.ly/3spLzqa

Today we interview Dr. Tom Beer, the Deputy Director of the Oregon Health & Science University Knight Cancer Institute, about COVID-19 transmission, policy, and vaccines. We also talk about olaparib. Back us on Patreon! www.patreon.com/plenarysession Check out our YouTube channel: www.youtube.com/channel/UCUibd0E2kdF9N9e-EmIbUew

In this episode, Charles J. Ryan, MD, and Neal D. Shore, MD, FACS, answer questions from a healthcare professional audience on topics related to prostate cancer and PARP inhibition including:Germline and somatic mutation testingManaging adverse events with PARP inhibitorsResistance to PARP inhibitorsImplications of monoallelic vs biallelic BRCA mutationsATM mutations and PARP inhibitor sensitivityPresenters:Charles J. Ryan, MDProfessor of MedicineB.J. Kennedy Chair in Clinical Medical OncologyDirector, Division of Hematology, Oncology and TransplantationDepartment of MedicineUniversity of MinnesotaOncologistDivision of Hematology, Oncology and TransplantationUniversity of Minnesota Health Clinics and Surgery CenterMinneapolis, MinnesotaNeal D. Shore, MD, FACSDirectorCarolina Urologic Research CenterAtlantic Urology ClinicsMyrtle Beach, South CarolinaLink to full program, including downloadable slidesets, expert commentaries, and on-demand webcast:https://bit.ly/2P31ZqF

In this episode, Jubilee Brown, MD, and Ursula Matulonis, MD, provide expert perspectives on new data from SGO 2021 presented for endometrial and ovarian cancer including:Results from KEYNOTE-775, a phase III trial of lenvatinib plus pembrolizumab in advanced endometrial cancerResults from the confirmatory phase III ARIEL4 evaluating rucaparib vs chemotherapy in BRCA-mutated relapsed ovarian cancer5-year follow-up from SOLO-1 trial of olaparib vs placebo in BRCA-mutated, newly diagnosed ovarian cancerLong-term follow-up results from the phase III ENGOT-OV16/NOVA trial of niraparib in patients with recurrent ovarian cancerOPAL: a phase II study evaluating dostarlimab, bevacizumab, and niraparib in platinum-resistant ovarian cancerPresenters:Jubilee Brown, MDProfessor and Director of Gynecologic OncologyLevine Cancer InstituteAtrium HealthCharlotte, North CarolinaUrsula Matulonis, MDChief, Division of Gynecologic OncologyBrock Wilson Family ChairDana-Farber Cancer InstituteProfessor of MedicineHarvard Medical SchoolBoston, MassachusettsContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3dAttwi 

In this episode, Michael J. Pishvaian, MD, PhD, and Rachna Shroff, MD, answer audience questions from a live CCO webinar focused on current best practices and emerging strategies in pancreatic cancer treatment, with questions including:What is your preferred regimen for neoadjuvant therapy in patients with resectable disease?How do you sequence therapy for patients with metastatic pancreatic cancer?How can you manage a patient who develops significant diarrhea with FOLFIRINOX?Are cisplatin and oxaliplatin equally efficacious for patients with BRCA-mutant disease?How should maintenance olaparib be used?Presenters:Michael J. Pishvaian, MD, PhD  Associate Professor of OncologyDirector, Gastrointestinal, Developmental Therapeutics, and Clinical Research ProgramsNCR Kimmel Cancer Center at Sibley Memorial HospitalJohn Hopkins University School of MedicineWashington, DCRachna Shroff, MDAssociate Professor of MedicineChief, Section of GI Medical OncologyDirector, UACC Clinical Trials OfficeThe University of Arizona Cancer CenterTucson, Arizona Content based on an online CME program supported by educational grants from Bristol-Myers Squibb and Ipsen Group.Link to full program:http://bit.ly/314BALT

This episode of PROSTATE PROS reviews and summarizes the year’s advancements in prostate cancer as well as looks forward to future updates. Beyond prostate cancer, the episode examines how COVID-19 has impacted the healthcare landscape and discusses news of the vaccine. Catch up on the latest and stay tuned for an exciting announcement. Liz:  [00:00] We have an exciting prostate cancer update.  Since recording this episode, the FDA recently approved the PSMA PET scan.  Keep that in mind when listening to the episode.  If you’d like further information, visit fda.gov. Dr. Scholz: [00:18] We’re guiding you to treatment success and avoiding prostate cancer pitfalls. I’m your host, Dr. Mark Scholz. Liz: [00:24] And I’m your cohost, Liz Graves. Dr. Scholz: [00:28] Welcome to the PROSTATE PROS podcast. Liz: [00:31] A lot has happened this year and we’ve covered many topics on the podcast. This episode we wanted to highlight a couple of exciting advancements and talk about some updates. Dr. Scholz: [00:44] The elephant in the living room of course, is the COVID situation. That’s impacted the way we do business. It’s impacted our patients. It’s impacted all of you dramatically. I thought I’d give a little update on what’s happened in our over 2000 clients. As you know, we serve a population of men between fifty and ninety plus our oldest patient just turned one hundred. This is a high risk group. Men are at higher risk for COVID complications and as we get older, particularly over 80, the complication rate goes up and the mortality rate goes up. We’ve actually lost one patient to COVID in our whole practice in 2020. It was an unfortunate individual that was traveling in Egypt in the January, February timeframe and when he came back to the United States he was ill. This was before people were really clear of what was going on, went to the hospital with pneumonia, and unfortunately passed away. We’ve had other patients, perhaps a dozen or so that have caught the COVID. They’re sort of evenly divided between men who really report that it wasn’t much of anything at all and others, the other half, they got pretty darn sick, a really bad flu. None of them fortunately had to go to the hospital. They all recovered. This is rather remarkable considering our vulnerable demographic. It shows that if people are careful and they isolate, they wash their hands, keep their hands off their face, most people aren’t going to catch this. Of course, when I talk to patients, I’m impressed by how much isolation is going on out there, how much care they are taking. Many men have come to the office and said that I am the first out of the house experience that they’ve had in 2020. So people are being very careful and clearly being careful does work. Liz: [02:49] Yeah. I remember early on in the pandemic, our office had way less traffic and was almost empty. Now it seems like things are picking back up and people are checking back in on their health. Dr. Scholz: [03:01] We’ve had a bunch of people come to the office who maybe had some cold symptoms, everyone’s on edge, and we’ve tested them for the COVID antibody to see if they did indeed have previous exposure. These tests are almost always coming back negative. We’re told by the scientists that these tests are probably 80% to 90% accurate. They’re not 100% accurate when you do the antibody test. That’s the test to determine if you’ve had previous exposure to COVID. We believe, and some people disagree, that if you’ve had previous exposure and your antibody test is positive, that it’s as if you’ve had a vaccination and you can’t catch COVID and you can’t transmit it. That of course would be good news. We’ve tested several hundred people now and almost all of them are negative. The ones that are positive are the ones that told us previously that they knew they had COVID. These antibody tests confirm it. This is a different test than the nasal swab, where doctors are trying to determine if you actively have the COVID virus. Those tests are more accurate, perhaps approaching 99% accurate. Patients who think that they have symptoms need to find a place to get tested, to rule in or rule out whether they are infectious. After they’ve been sick, they want to be tested again, to make sure that the infection risk has gone away. Liz: [4:38] We’ve had inquiries about where to get tested. We usually just send whoever across the street to Cedar Sinai, and they’ll do it there. The turnaround on these test is quick enough that people can just wait for their results and they should know within an hour. All right, Dr. Scholz, I think the biggest information about COVID right now is news of a vaccine. I think one thing a lot of people are concerned about is how quickly this has developed vaccines usually take years, if not a decade to get developed. This has happened within a year, which is pretty incredible. Do you think it will be safe? Dr. Scholz: [05:15] So there’s been debates, everyone’s heard them, that will the vaccine work, will it have durability? At this point, the preliminary science suggests that it will work and it will have durability. There’s three different companies that are putting forth a new product. The hope is that by the end of the year we will be having people getting vaccinated. Of course, there’ll be selective preference for the elderly people in healthcare. How this is all going to roll out is a big question. But it seems at this point, there’s no doubt that by early 2021 a vaccine is to be available and it will be effective. Liz: [06:00] It is changing really quickly. I know we were just talking about this last week and when I went back to review, I almost had to research it all again. So it’s important to stay up to date on this. Dr. Scholz: [06:14] Yeah everything that we do in the oncology realm and in this realm as well is predicated on what we call a risk-benefit ratio. We give dangerous medicine sometimes in oncology, but we are treating life-threatening cancers and sometimes rolling the dice and taking a chance with a treatment makes a lot of sense if the disease is much worse and very dangerous. So it’s going to be different for different people, for myself as a physician, meeting people all day long and basically in a high-risk situation, it seems to me that I’ll be lining up early for the vaccination. For those of you out there that are comfortable in your isolated state and are willing to sustain that, 2020 showed us that people can remain pretty safe if they’re very careful, but the social isolation is taking a big cost in our patients’ mentalities, their lifestyles, their social lives. It’s been painful and difficult when people have to make a personal choice as to whether the relatively small risk of getting a vaccine is too great to consider as opposed to continuing in their existing lifestyle. We’ll have more information every month as this vaccine rolls out as to how dangerous or how many risks there’ll be associated with it. That is unknown at this point. But as a lot of people are going to be getting this vaccine, we should have very good information within a few months. I think one last thing to emphasize is that we’ve learned that the COVID virus complication rate goes up astronomically in men over 80. Men over 80 and the elderly are at the very highest risk and mortality rates start to become very significant in this group. It would seem to me that these elderly men are going to want to try and get a vaccine, even if there are some risks associated with the vaccine, because the virus for them is very dangerous. Liz: [08:22] So another paradigm shift that occurred this year was the shift towards telehealth. It seems like about half of our visits now are being conducted over the phone or via FaceTime or Skype. Dr. Scholz: [08:36] This has been a really big change. In trying to understand it and wrap my brain around it, it seems that it’s a radical shift in accessibility. In the past, phone visits were discouraged because the impetus was to get people into the office and be able to bill for your services. Now, both private and Medicare insurance has essentially mandated insurance coverage for telehealth. This has rapidly been accepted by patients due to the accessibility, the ease of communication. It’s even been nice to be able to take off my face mask and see the body language of my patients and communicate non-verbally with Skype and FaceTime. In the office employees, patients alike are all wearing masks and we’re making eyes at each other, using our voices and trying to overcome the muffled communication that has become routine now in our lives. Liz: [09:44] I think something else that the telehealth has brought is connection. Right now people are feeling kind of anxious and separated. If they are skipping doctor’s appointments to avoid waiting rooms and being close to other people, it’s such a great way to catch up on the latest in prostate cancer and catch up with you. Your face appears in their living rooms and it’s like they’re right in your office. Dr. Scholz: [10:10] Yeah it is very personal. It’s as you all have experienced now, your face fills the screen and it’s not as disconnected as people might think. The risk to patients with telehealth is obviously reduced. But one component of the way we do medicine, of course, is blood tests, injections, and treatments, and certain in office visits are still unavoidable. If patients go to a remote facility for blood testing, they’re still going to have some contact. But so far as has been demonstrated, the COVID infection rate for our patients has been very low, whatever precautions people are taking seem to be working quite well. One thing about telehealth is it appears to be here to stay. I’ve talked to high-level insurance people about the future of telehealth asking, will it go away once the COVID risk disappears? The general consensus is that there’s no going back. This increased accessibility seems to be the future of medicine. Liz: [11:19] So even big topics that are maybe a little more involved or confusing are easily addressed over Skype or FaceTime or a phone appointment. Let’s start talking about a couple of those that are new developments for 2020. Dr. Scholz: [11:34] We already covered PARP inhibitors but they, being brand new treatments for advanced prostate cancer, merit a quick review. PARP is an enzyme that helps repair DNA. About 10% to 15% of men with advanced prostate cancer have a mutation that causes their DNA repaired to work less efficiently. One application of this mutation, which is called BRCA, is that there’s a little higher risk of getting prostate cancer. The men who get prostate cancer that have BRCA tend to have a more aggressive form. The PARP inhibitors exploit this mutation and men that have this mutation respond much, much better to PARP inhibitors. PARP inhibitors are pills that make it even more difficult to replicate or duplicate DNA. These already impaired cancer cells then die more easily and more quickly than your normal cells of your body. We’re always looking for a differential effect with cancer treatments, a treatment that focuses more on the cancer, then your cells killing cancer without causing a lot of side effects. So the medicines we’re talking about are Olaparib and Rucaparib two new pills that help men with BRCA mutated cancer and are now FDA approved. Liz: [13:01] These two approvals really highlight how important using genetic testing is. This will help men with prostate cancer find treatments that may have only been FDA approved for another cancer. Doing genetic testing is very easy. It can be accomplished with a mouth swab or a blood test, and it’s almost always covered by insurance. So we briefly covered some updates and genetic testing. Let’s review the PSMA PET scan really quick. Dr. Scholz: [13:32] We did a whole podcast on this because it’s a big breakthrough. Most of you have heard of it by now, but for the first time we can accurately locate the prostate cancer wherever it is in the body and the prostate and the lymph nodes in the bones with one single scan. This scan may be five times more accurate, ten times more accurate than any previous scan that was available. What a wonderful addition to our diagnostic armamentarium. This is going to have an impact for people with early stage disease, late stage disease. Unfortunately, the FDA has not yet approved it, but we’re anticipating approval within the next six months or so. In that situation, it will be covered by insurance and it will be very popular. Liz: [14:18] Some companies are investigating using PSMA as a therapeutic target rather than just a diagnostic target. Dr. Scholz: [14:28] Exactly. So the diagnostic scanning is incredibly useful reconnaissance for figuring out where the cancer is and helping design a treatment protocol. But if we’re able to accurately locate the cancer with these scans, wouldn’t it be possible to use this same target, to make therapies stick to the surface of the cancer cells? There are two very exciting types of treatment. One we’ve talked about before uses an antibody to stick to PSMA and draw a high energy radioactive molecule right next to the cancer cell and kill the cancer cell. This is called Lutetium- 177. The phase three trials in prostate cancer have been completed. We’ve had patients on trial or outside the country, get this treatment with very nice responses. We’re talking about a treatment for men that have already had chemotherapy, become hormone resistant to Zytiga and Xtandi, and who perhaps have limited treatment options getting nice PSA declines with relatively little, if any, toxicity. There is a PSMA antibody on the salivary glands, so some people get a little bit of a dry mouth. Some people with radiation, it can cause some lowering of blood counts, but for the most part, there’s practically no side effects with dramatic responses to Lutetium-177. The phase three trials are completed and they’re waiting for them to mature to validate that there is a survival advantage. Once that happens and the study results are released, the FDA has six months to approve or disapprove the treatment for broad spectrum dispersal amongst the population for therapy and insurance coverage. Liz: [16:14] So it seems like there’s a lot to look forward to with PSMA being used as a diagnostic test as well as its role in therapeutics, especially for men with advanced prostate cancer. There are a couple immunotherapies that are exciting on the horizon. Can we talk a little bit about those? Dr. Scholz: [16:36] Amgen has developed a connector molecule that instead of linking a radioactive moiety to the antibody that clips to PSMA, it’s sort of like a pheromone tag that draws in your T-cells. I don’t know how many of you are familiar with how the immune system works, but the soldier cells of the immune system are called the T-cells and the T-cells are the component of your immune system to go in and attack the cancer cells and kill them directly. Theoretically, if you can get the T-cells in close approximation with the cancer cells, they will attack and kill them. There is new technology from Amgen, a very large pharmaceutical company, that has developed this and is doing phase two testing in men with advanced prostate cancer and responses are indeed occurring. So the patients are injected with a substance that clips onto PSMA i.e. the surface of the cancer cells and draws the patient’s immune system close to the cancer cells so that it will attack it. Liz: [17:49] As you can see, there’s so much information about prostate cancer this year alone, we’ve covered focal therapy, brachytherapy, radiation, immunotherapy, chemotherapy; the list goes on and on. So looking forward, it’s important to always stay in touch and stay up to date and keep sharing and keep listening. You might find it useful to go back and review old episodes of PROSTATE PROS. You can find us on your favorite player. So Dr. Scholz, another exciting thing 2020 was the 10th anniversary of your first book Invasion of the Prostate Snatchers. Something you may not know is that this year, Dr. Scholz and I have been working hard to update his first book Invasion of the Prostate Snatchers. So about 10 years ago, when the first edition was published, it was really the first introduction to active surveillance. I think Dr. Scholz received a little flak from that, and now it’s more widely accepted, but with that, there’s still a lot of the industry that patients need to be careful of. That includes over-treatment. That includes dangers of surgery and random biopsies. So we’re really looking to restart the conversation, and get patients to be their own advocates. Dr. Scholz: [19:16] There’s a theme in the prostate cancer world that you have to educate yourself. I hope that both of my books encourage people to do their own research, to take responsibility for their health and to double check the information, rather than just accepting the first pitch you hear from a doctor. Prostate cancer is big business. It’s a multi-billion dollar world, and people are trying to make a profit. Ethically, no doubt, there’s so many gray areas in the prostate cancer world. You need to double-check and you need to find the original, basic information that leads you to the truth. Liz:  [19:59] So this new completely rewritten second edition of Invasion of the Prostate Snatchers will be out in 2021.  We’re really excited to share it with you.  Telehealth has really connected us this year, and we’re looking forward to staying connected in 2021.  Remember to tune into the podcast and share with your friends.  If you have any topics you want us to cover in the upcoming year, you can email us at podcast@prostateoncology.com.

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

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

Listen to Prof Nicoletta Colombo and Bradley J. Monk, MD, FACS, FACOG, discuss current best practices for biomarker testing for your patients with advanced ovarian cancer.In this episode, Prof Nicoletta Colombo and Bradley J. Monk, MD, FACS, FACOG, discuss current best practices for biomarker testing in the management of patients with advanced ovarian cancer. Topics include:Subtypes of ovarian cancerBRCA mutation testing Homologous recombination deficiency testing Presenters:Professor Nicoletta ColomboProfessor of Obstetrics and GynecologyUniversity of Milan-BicoccaEuropean Institute of OncologyMilan, ItalyBradley J. Monk MD, FACS, FACOGProfessorDivision of Gynecologic OncologyArizona Oncology (US Oncology Network)University of Arizona College of Medicine--PhoenixCreighton University School of Medicine at St Joseph's HospitalPhoenix, ArizonaContent based on an online CME program supported by an educational grant from GlaxoSmithKline.Link to full program:https://bit.ly/2Scnp2N

In this episode, Isabelle Ray Coquard, MD, PhD and Bradley J. Monk, MD, FACS, FACOG, discuss current first-line maintenance therapy options for patients with advanced ovarian cancer. Presenters:Prof Isabelle Ray CoquardProfessor of Department of Medical OncologyClinical Science Institute of the Léon Bérard CenterLyon, FranceBradley J. Monk MD, FACS, FACOGProfessorDivision of Gynecologic OncologyArizona Oncology (US Oncology Network)University of Arizona College of Medicine--PhoenixCreighton University School of Medicine at St Joseph's HospitalPhoenix, ArizonaContent based on an online CME program supported by an educational grant from GlaxoSmithKline.Link to full program:https://bit.ly/2Scnp2N  

An interview with Dr. William P. Tew from Memorial Sloan Kettering Cancer Center on “PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline.” This guideline provides recommendations on the use of poly (ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer. Read the full guideline at www.asco.org/gynecologic-cancer-guidelines. Transcript The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. William P. Tew from Memorial Sloan Kettering Cancer Center in New York, New York, lead author on PARP inhibitors and the management of ovarian cancer. Thank you for being here, Dr. Tew. Thank you, Brittany, for having me. First, I'd like to note the 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 full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Tew, do you have any relevant disclosures that are directly related to this guideline topic? No, I do not. OK, thank you. Then, can you give us a general overview of what this guideline covers? Sure. So my co-chair, Elise Kohn, and panel members, and ASCO staff put together a very comprehensive guideline on the use of PARP inhibitors in the management of women with ovarian cancer. And as many of your listeners may know, there has been a rapid speed of phase 3 practice changing trials that have been published and FDA approvals within the last year, and what we wanted to do was to put that all in one document and give guidance on how and when and which PARP inhibitor to use in your specific patient and at what point during the lifecycle of ovarian cancer of when to use it. So we broke up the guideline into five sections. One is the use of PARP inhibitors as maintenance therapy after first line platinum based treatment in women with stage 3 and 4 ovarian cancer. Second, we looked at maintenance therapy after a second or higher platinum based treatment. Three, the use of PARP inhibitors as treatment for patients with recurrent epithelial ovarian cancer. We then looked at different combinations of PARP inhibitors, whether it's with chemotherapy or biologics and the data that we have presently on those combinations. And then lastly, we looked at common side effects with PARP inhibitors and offering guidance on how to manage those toxicities. Great. Then you just mentioned that this covers several different sections, so I'd like to go through each of those sections and review those recommendations for our listeners. So first, what are the recommendations for PARP inhibitors for patients with newly diagnosed epithelial ovarian cancer? So for women with newly diagnosed ovarian cancer, there's been several studies that have been published in the last year and a half, and we broke this up into the different studies and the different patient populations. First and foremost, we wanted to stress that PARP inhibitors are not recommended for the use in the initial treatment of patients with early stage, meaning stage 1 or 2 ovarian cancer, because there really isn't sufficient evidence to support the use in this population. All of the trials looked at patients with stage 3 or 4 epithelial ovarian cancer and used primarily in the main setting, and what that basically means is that women that have had a complete or partial response to first line platinum based chemotherapy and have response by CT scan or CM 125, when do you use a PARP inhibitor? Which are the women that you would say PARP inhibitor is going to benefit you with long-term outcome? So our first recommendation is based on a trial-- looking at a drug called olaparib. Olaparib was the first PARP inhibitor published in this population, and in that study, they included women with both germline or somatic pathogenic or likely pathogenic variants in the BRCA1 or BRCA2 gene. And so this is a group of women that you could offer olaparib for. And generally, that is given at a dosage of 300 milligrams once every 12 hours for up to two years. The second study looked at a drug called niraparib, and in this trial, they included population of all women, regardless of BRCA status. And they offered it to women with high-grade serous or endometrial ovarian cancer. And the FDA has given approval for the use of niraparib for all patients, and that is at a dosage of 200 to 300 milligrams oral daily for three years, with the lower dose given for patients who have a low platelet count or low body weight to prevent the common toxicity of thrombocytopenia. Then you could consider longer durations in select individuals, but generally, these drugs are given for a limited period of time and continued unless a patient has significant toxicity or progression. The other two studies in the newly diagnosed ovarian cancer population was a study that looked at olaparib with bevacizumab maintenance. This was a study that included patients with germline or somatic mutations and BRCA 1 or 2 and/or genomic instability or homologous repair deficiency, as determined by the myriad my choice test. And again, this population, a partial or complete response to chemotherapy and their first line therapy should have included bevacizumab. And so if one is on bevacizumab with their platinum based therapy, they should have a response to treatment, one could continue bevacizumab and add the addition of olaparib as a PARP inhibitor. And then the final study that we addressed was called switch therapy, and that we don't really have enough data to support its use, specifically that's with the drug called veliparib, and veliparib was given in addition to the chemotherapy and then continued as a maintenance therapy. We don't really have sufficient data to suggest this was superior, equal, or less toxic than the approaches discussed above, which is single agent PARP inhibitor or bevacizumab with PARP inhibitor. And it should be noted, also, veliparib is not yet an FDA approved drug and not commercially available. OK, then what are the recommendations for PARP inhibitors for patients with recurrent epithelial ovarian cancer? Yeah, and this data has been around a little bit longer, and I think any oncologists that treat them with ovarian cancer are more comfortable with the evidence with these studies. So what we're talking about here is that patients who were in clinical remission and then their ovarian cancer recurs. And the first group of women that we look at is patients that are then retreated with platinum based therapy. Those women that have platinum sensitive disease, and then whether to offer PARP maintenance in the second line or more remission settings. And there is very good data to support the use of PARP monotherapy in second or greater maintenance. This has been shown with all three commercially available PARP inhibitors, olaparib, rucaparib, and niraparib. We do know that women who have a germline or somatic pathogenic or likely pathogenic variant in the BRCA 1 or 2 genes have the highest benefit of maintenance PARP inhibition, and those patients have the strongest evidence to receive those drug. So the only other point I wanted to make with current ovarian cancer is if a patient has received a PARP inhibitor in the past, there is no evidence to give a second exposure to PARP inhibitor. Those studies are being developed now, but PARP inhibitor use once in the life cycle is what's recommended. And then there's also evidence to use PARP inhibitor as an actual treatment. So not in the maintenance setting, and the drug most commonly used as one called niraparib or olaparib, and these are patients that have measurable disease or generally have platinum sensitive disease, and those women that have homologous repair deficiency, as determined by the Myriad myChoice test, and again, have platinum sensitive to disease do have benefit for treatment with PARP inhibitors. OK, then, so you just mentioned this, but is it correct that PARPi therapy for epithelial ovarian cancer should not be repeated over the course of treatment? Right now, that is what we recommend. All of the studies that looked at the use of PARP inhibitors disqualified women who have had prior PARP inhibitors. So as of now, we don't have any evidence to support the use of repeated PARP inhibition. And what does the guidelines say about using PARP inhibitors in combination with chemotherapy or other targeted agents? There are many studies going on currently looking at the use of PARP inhibitors in combination with immunotherapy, chemotherapy, and other targeted agents, but currently, at least in the recurrent setting, there is no data to support its use in combination with another anti-cancer treatment. Now, of course, in the context of a clinical trial, this would be very reasonable, and we encourage clinical trial participation. The only studies that looked at PARP in combination with other anti-cancer treatments are in the first line setting, as I discussed earlier, including PARP inhibitors with bevacizumab, as in the case with olaparib or PARP inhibitors with chemotherapy, as is often the case with veliparib. OK, thank you. And then how should clinicians manage the adverse effects associated with PARP inhibitors? I think the first and foremost thing is to be aware of the specific side effect profile of each PARP inhibitor, because they can vary slightly between parts. The most common side effects include fatigue, nausea, change in appetite, and effects on the blood counts, and we gave guidance on each of those specific side effects. As far as the effects on the blood counts, anemia, I'd say, is one of the more common side effects across all PARPi's, and the use of blood transfusions is generally recommended if patients are symptomatic and their hemoglobin is below 8 to 7. And then for neutropenia, usually, this requires hold of dosing, and we did not encourage the use of growth support, although it may be used in certain settings when the drugs on hold. And then the final cytopenia issue is the issue with platelets, and this is unfortunately very common side effect with niraparib. And we discussed earlier about starting at a lower dose, 200 milligrams of niraparib based on a weight and platelet count to help temper the degree of thrombocytopenia. But with thrombocytopenia, clearly, the drugs sometimes need to be held or discontinued if it's significant. And with cytopenias, we do recommend close observation of laboratory blood work, particularly in the first month of use of PARP inhibitors, and then always being mindful if patients are on PARP inhibitors for prolonged periods of time that there has been reports of treatment related myelodysplastic syndromes and leukemias and that should be further worked up if there is any evidence of dysplasia. So then, what is the importance of this guideline in your view, and how will its implementation affect clinical practice? Well, I think this is the most up-to-date and comprehensive guideline on PARP inhibitors and will help, both clinicians and patients, understand all the practice changing studies, the populations, and the settings they will use, and all these studies that were published over the last five years. I think this last year we've seen such a rapid growth of clinical trial results and FDA approvals that this manuscript, I think, successfully puts them all together in table form and brief recommendations to better treat and provide proper management to your patients with ovarian cancer. And then finally, how will these guideline recommendations impact patients with ovarian cancer? We were very fortunate to have two patient advocates as part of our panel, and what they told us was that these recommendations will help them understand the scientific trials, will put in context when to use PARP inhibitors, and also to prepare them for those conversations that they have with their clinicians in discussing if they're a good candidate for a PARP inhibitor now or in the future. So we're really proud of that, that we were able to get our patients perspective in developing these guidelines. Definitely. Well, thank you for your work on these important and timely guidelines and for taking the time to join me on the podcast today, Dr. Tew. My pleasure. Thank you so much, Brittany, for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. 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, available on iTunes 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.

What were the practice-changing studies presented at the 2020 ASCO Annual Meeting? Podcast host David H. Henry, MD, and retired oncologist Alan P. Lyss, MD, reviewed 12 studies and assessed their potential impact on treatment.  Breast cancer Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. (Abstract 501) The addition of anthracyclines did not improve event-free or overall survival. The results suggest patients can avoid the toxicities of anthracycline regimens without compromising efficacy, Dr. Henry said. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. (Abstract 1000) Pembrolizumab improved responses, particularly in patients with higher PD-L1 expression. Dr. Lyss noted that pembrolizumab was combined with a “broad range” of chemotherapy regimens in this study.   A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). (Abstract LBA2) Early local therapy did not improve disease-free survival or overall survival. “We probably should not be recommending planned treatment for the intact primary tumor in most women who have stage IV breast cancer,” Dr. Lyss said. Bladder cancer Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. (Abstract LBA1) Avelumab maintenance prolonged overall survival, although 12% of patients discontinued the treatment due to toxicity. Because avelumab “meaningfully prolongs overall survival … using it upfront makes a lot of sense,” Dr. Lyss said. Colorectal cancer Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. (Abstract LBA4) Pembrolizumab improved responses and progression-free survival. All patients with colorectal cancer should be tested for microsatellite instability-high status “because these results really do influence practice immediately,” Dr. Lyss said. He suggested that pembrolizumab should probably be used as first-line treatment for these patients even though overall survival results are not yet available.   Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: The randomized RAPIDO trial. (Abstract 4006) Short-course radiotherapy followed by consolidative chemotherapy and surgery significantly reduced the rate of treatment failure. Dr. Lyss called the pathologic complete response rate “impressive” and said it may contribute to a higher rate of rectal preservation.   A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone for liver metastasis from colorectal cancer: JCOG0603 study. (Abstract 4005) There was no improvement in overall survival with mFOLFOX6. “The take-home to me … is this is probably not a necessary strategy and certainly not standard of care,” Dr. Henry said.   Hodgkin lymphoma KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). (Abstract 8005) Pembrolizumab improved progression-free survival. Dr. Henry marveled that pembrolizumab bested brentuximab vedotin, which previously produced impressive results in patients with relapsed/refractory Hodgkin lymphoma. Lung cancer Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. (Abstract 9500) Nivolumab plus ipilimumab improved overall survival but increased toxicity and treatment discontinuation. The combination is “not for the faint hearted” but is appropriate for certain patients, Dr. Lyss said, noting there is “room for clinical judgement.”   Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. (Abstract LBA5) Osimertinib improved disease-free survival compared with placebo. It isn’t clear how osimertinib will impact overall survival, but “we should be using this drug” once it’s approved, Dr. Lyss said.   Smoking cessation (SC) and lung cancer (LC) outcomes: A survival benefit for recent-quitters? A pooled analysis of 34,649 International Lung Cancer Consortium (ILCCO) patients. (Abstract 1512) Quitting smoking can improve overall survival in lung cancer patients, even if they quit as little as 2 years prior to diagnosis. “Somewhat counterintuitively, convincing patients to quit smoking at any point in their trajectory, even just prior to their diagnosis, seems to make a difference in survival,” Dr. Lyss said.   Ovarian cancer Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. (Abstract 6002) Olaparib maintenance improved overall survival and time to next treatment. Significant benefits were seen in the olaparib arm in spite of a high rate of crossover, Dr. Henry noted. *  *  *   Disclosures: Dr. Henry, of Penn Medicine in Philadelphia, reported having no financial disclosures relevant to this episode. Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. He is a columnist for MDedge Hematology/Oncology. He has no other conflicts of interest. *  *  *   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

This week we have an announcement -- the audiobook of "Malignant: How Bad Policy and Bad Evidence Harm People with Cancer", written and narrated by our host Vinay Prasad, is available now on Amazon, iTunes, and Audible! We also have an in-depth journal club for you on the findings of the PROfound trial as published in a new paper out in the New England Journal of Medicine titled "Olaparib for Metastatic Castration-Resistant Prostate Cancer". Finally, we end the episode with an interview with Dr. Adam Cifu of the University of Chicago on literature, medicine, maintaining a feeling of normalcy and self during COVID-19, and more! Listen to Malignant with a free 30-day trial of Audible: https://www.audible.com/pd/B08864KFHW/?source_code=AUDFPWS0223189MWT-BK-ACX0-195112&ref=acx_bty_BK_ACX0_195112_rh_us PROfound: doi.org/10.1056/NEJMoa1911440 Crossover: doi.org/10.1093/annonc/mdy116 Back us on Patreon! www.patreon.com/plenarysession

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.  Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer. This podcast will be led by Dr. Brian Shuch, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta (Monty) Pal. Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck. Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb and Exelixis. View full disclosures for Dr. Shuch, Dr. Agarwal, Dr. Grivas, and Dr. Pal at Cancer.Net. Dr. Shuch: Hi, I'm Dr. Brian Shuch from UCLA's Institute of Urologic Oncology. And I'm really thrilled to moderate today's Cancer.Net podcast on GU clinical trials. I'm joined today by Dr. Neeraj Agarwal from Utah's Huntsman Cancer Center, Dr. Petros Grivas from the University of Washington's Fred Hutch Cancer Center, and Dr. Sumanta Pal from the City of Hope Cancer Center. Thanks for being here today, and we'll jump in to discuss 3 clinical trials in the urologic cancer space, one for prostate, one for bladder, and one for kidney cancer. Let's discuss some of the goals of clinical research first, okay? Neeraj, can you let us know what is the purpose of a clinical trial, and the ultimate goal? Dr. Agarwal: All these clinical trials aim to identify better treatments with the hope that the treatment will be safe and effective. An ultimate goal for all the clinical trials is to get approval [from the FDA for the routine use of the new treatments being tested.] I'd like to add, that the way I explain this to my patient, a clinical trial is the only way I can get cutting-edge therapy for my patients in my clinic without having to wait for many years for FDA approval of those drugs. Dr. Shuch: Petros, it seems that patient engagement is really essential to this type of clinical research. What is the patient's role here, and what can they expect by participation in a clinical study? Dr. Grivas: They can directly help [the research team] define better treatments and also improve existing therapies. And they can do that by either participating in clinical trials directly, and can also help us find the clinical questions. And the patient advocate groups are helping us do that by giving us input how to design clinical trials. And, of course, a number of trials that we're conducting are focusing on disease prevention or treatment of the cancer. And I think the patient's role overall is critical in every patient who's asked their provider about clinical trials. Dr. Shuch: So Monty, for your patients, how do you ensure patients are safe when they participate on these types of trials? Dr. Pal: Safety is our primary concern when conducting a research study. The patients are taking risks by participating, and these risks should be very clearly delineated in the context of a consent form. It's really critical that we, as investigators, perform very close monitoring in association with our patients. But we also have very intensive oversight of our clinical trials by independent monitoring committees, by the drug companies, and even the FDA. Now, trials can actually be closed early if there are safety concerns that emerge, or if drugs don't appear to be effective. Keep that in mind. Dr. Shuch: Got it. It's reassuring that for these types of trials, there's very close monitoring. So Petros, with the potential risk that we discussed, why would a patient participate? What are the benefits here? Dr. Grivas: Brian, this is a critical question. And I think the purpose of cancer research and clinical trials is to try to benefit the patient individually, but also to try to move the field forward, in terms of more knowledge about cancer research, also benefit the community and the society, in general. Dr. Shuch: How does a patient identify if a clinical trial's right for them? And how can they potentially participate? Dr. Agarwal: I think the most important role is of the physician who is seeing the patient. And the physician may alert you to a specific clinical trial that is focused on your current condition. So maybe 10 or 15 or 20 clinical trials you saw on the Huntsman Cancer Institute website, but maybe 1 or 2 are specifically needed for a patient's given situation. Also, not every center has a clinical trial for every condition. Dr. Shuch: We’ll jump in to discuss 3 clinical trials that were chosen by members of Cancer.Net editorial board for genitourinary cancers. And they were basically chosen from the Trials in Progress abstracts that were submitted and presented at the ASCO GU 2020 Symposium. So because these are ongoing clinical trials, we may not have final results for these trials at this time. But I'd like to note that none of the members of this discussion have any direct involvement for these trials. For reference, all relevant disclosures can be found on the notes for this episode of Cancer.Net. So let's jump in. Neeraj, let's discuss the KEYLYNK-010 study. [Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010) (KEYLYNK-010)] Can you briefly summarize this study for us? Dr. Agarwal: So this study is for patients who have progressive metastatic castrate-resistant prostate cancer, meaning the metastatic prostate cancer or advanced prostate cancer, which has already progressed on multiple previous lines of therapy, including chemotherapy and 1 of the novel hormonal therapies, which include enzalutamide and abiraterone. These are all standard therapies which are approved currently by FDA for treatment of our patients. Before I talk about this clinical trial, which includes multiple drugs, which is basically testing a combination of immunotherapy, pembrolizumab, with olaparib, which is a PARP inhibitor—and I'm going to explain those drugs in a moment—and comparing these drugs with other drugs, which are already approved by FDA and include enzalutamide and abiraterone. These drugs are manufactured by Merck, AstraZeneca, Pfizer, and Janssen. And I have consulted on a scientific advisory boards to all these companies and received honoraria for consulting to these companies.  So with that in the backdrop, I'd like to go ahead and briefly summarize this study. The patients who are progressing on the standard treatment option for metastatic castrate-resistant prostate cancer, including prior chemotherapy, and 1 of these novel hormonal therapies, which include abiraterone or enzalutamide, but not both, these patients are randomized on a 1-on-1 fashion to the novel combination of pembrolizumab with olaparib versus other hormonal therapy, which the patient has not received in the past. The patient's disease has progressed on abiraterone or enzalutamide. Then they are randomized to the novel combination pembrolizumab with olaparib versus abiraterone or enzalutamide. Dr. Shuch: So Neeraj, what's the current standard of treatment for these patients at this time? Dr. Agarwal: The current options are very limited. I would say the only chemotherapy, which may be used again, is docetaxel. Sometimes, we re-treat patients with 1 of these drugs on which they have already progressed. Cabazitaxel is another drug which can be used. But please note that by the time patients have already had disease progression on these previous therapies, the expected benefit by trying these currently available options are very limited. Most of the time, patients experience disease progression within 3 to 4 months on these currently-approved medications. Dr. Shuch: So what is the exact problem that you're trying to solve or show with this study? Dr. Agarwal: So pembrolizumab is an immunotherapy, and it’s already approved for patients with multiple types of cancer. Olaparib is an oral pill which is already approved for patients with advanced breast cancer and ovarian cancer. Olaparib works by incapacitating the cancer cells from repairing their DNA, which in turns lead to cancer cell death. Taking a step back, if when we treat patients with olaparib, these cells also get unusually sensitive to action by concomitant treatment with immunotherapy. And this is based on the laboratory data, pretty strong laboratory data. And hence, there is a rationale for combining pembrolizumab with olaparib. And what olaparib is doing is, it is killing the cancer cells by incapacitating them from repairing their DNA, and simultaneously making them very sensitive to action by immunotherapy. And then we are using pembrolizumab at the same time, which is immunotherapy, and hence we expect these 2 drugs to synergize, and lead to an exponential increase in cancer cell death.                 Dr. Shuch: So Neeraj, so it sounds like there's pretty strong scientific rationale. But what question does this study aim to answer? Patients want to live longer? They want to be more stable on therapy? Dr. Agarwal: The study has 2 major primary endpoints, which basically means 2 major questions the study is asking. Number 1 is, are patients going to live longer when they receive this novel combination versus standard therapy? And secondly, are they going to respond for [a] longer time, meaning they will have a longer duration of disease control defined as the radiographic progression-free survival. That is another primary endpoint of the study. So the study is asking whether patients are living longer, with better control of their disease with this novel combination. Dr. Shuch: So Neeraj, with this new approach, are there any specific risks that patients would want to know about for this type of study? Dr. Agarwal: Pembrolizumab is already FDA-approved for more than 10 different kinds of cancers at least. This is an immunotherapy, which basically up-regulates our immune system in a rather non-specific way. Most of the patients, the vast majority of patients take pembrolizumab very well with minimal side effects. But then a small minority of patients, I would say somewhere around 4 to 5 percent, patients have hyper activation of the immune system, which can attack our own organs. So the most common side effects with any immune checkpoint inhibitor like pembrolizumab include diarrhea, liver toxicity, skin toxicity, and less frequently lung toxicity, or attack of immune system on the endocrine glands. These are only some of the toxicities which we usually see on our clinic, but it doesn't mean other rare toxicities may not happen. So these drugs require close monitoring. They're given every 3 weeks. So pembrolizumab, especially, is given every 3 weeks. And it is very important that patients are seen regularly by their oncology providers, so that if there are any of these toxicities are happening, they can be controlled at a much earlier stage, rather than becoming very severe and being picked up at a more severe stage. So I just want to add the toxicities of olaparib, which is already approved for patients with breast cancer and ovarian cancer. So we are not talking about any experimental drugs here for human beings. Both of these drugs are approved for various cancers already, with very well-defined toxicity profile. The combination is unique. Combination is being tested for the first time. So olaparib can cause bone marrow suppression, which basically means it can lead to anemia, low platelet counts, and low neutrophils, which are the defense cells fighting for us against infection. Most of these toxicities are easily manageable by modifying the dose of olaparib.  Dr. Shuch: Neeraj, it sounds like this could be a really important study, and we'll keep an eye out for future updates. Please keep us posted. So let's move on to some of the exciting kind of work in bladder cancer. Petros, can you discuss this ongoing study that was presented at ASCO GU, the KEYNOTE-866 protocol? [Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866) (KEYNOTE-866)]  Dr. Grivas: Sure. Before I start, I want to say that I have done consulting with this trial sponsor, which happens to be Merck, for unrelated reasons and not for this trial.  And this trial is open in our institution, but I'm not involved directly into that study. This particular clinical trial is trying to evaluate the following question. Right now, the standard of care for patients who are aiming to go for removal of the bladder—we call this radical cystectomy—is to get chemotherapy with the regimen consisting of gemcitabine and cisplatin combination chemotherapy before cystectomy. We call this pre-operative, before the operation, or neoadjuvant cisplatin-based chemotherapy. And that's a standard of care in patients who are fit enough to tolerate this study, because this study can cause side effects. So the question is, can you now use immunotherapy, in particularly this drug called pembrolizumab, which is activating the immune system, in combination with chemotherapy. So chemotherapy plus, pembrolizumab, as compared to chemotherapy plus placebo before patients get cystectomy, removal of the bladder. Dr. Shuch: So these are patients who are going to go for surgery? Dr. Grivas: That is correct. This patient population are those patients who have made a decision to go for removal of the bladder, and we call this, as I mentioned, radical cystectomy. And I mention this because there are some other treatment approaches. Dr. Shuch: The current standard of care is chemotherapy and then surgery. So what is the problem that the researchers are trying to solve? Dr. Grivas: The main question is, does the addition of this immunotherapy to chemotherapy increases chance and [the likelihood of] not finding any residual cancer when the bladder is removed, and whether it actually increased the time of being cancer-free and alive down the road. So does the addition of immunotherapy to chemotherapy improves how these patients do over time, in terms of less of cancer recurrence, meaning cancer coming back, and longer life? Dr. Shuch: Okay. So you want to see the tumors disappear, and then you want to prevent patients from having recurrences with this study. Dr. Grivas: That is correct, and ideally, live longer, if possible. Dr. Shuch: And how was it specifically designed? What was the rationale with this type of approach? Dr. Grivas: Brian, this is an important question because we have to use previous information to inform the design of those trials. And I would mention that there are some observations about chemotherapy and immunotherapy combinations might work well in other cancer types. And particularly, in patients with bladder cancer, there were a few previews, smaller-sized clinical trials that showed promising results, meaning higher chance of making the cancer disappear when they take the bladder out. And because those trials were very promising and also showed that the combination of chemotherapy and immunotherapy was feasible, then the bigger trials now being launched to confirm the results and compare this combination with the standard of care right now. So strong previous data supports this larger trial to evaluate whether this addition makes sense. Dr. Shuch: So, Petros, patients generally are going to go to surgery. You're giving them a different medication, immune medication. What would be additional risk that patients would have with this approach? Dr. Grivas: So every time you add a new therapy, there is a chance of side effects as Dr. Agarwal mentioned before. And particularly, when you add immunotherapy, there is a small but real chance of having immunotherapy-related adverse events. And that's what we call side effects from a very activated active immune system. And I think it's important to have this discussion with the patient about benefits or risks before the trial starts. And before the patient makes a decision. Overall, these immunotherapy-related adverse events usually, as I mentioned, are not very common, especially when we compare the immunotherapy with the chemotherapy. However, we have to be very careful, especially with a combination. And these patients are monitored very closely for any side effect that might happen. And I think education is important for both the patient and the medical provider team, how to monitor and do a close observation for those side effects. The side effects of chemotherapy are standard. And that is something that's also a part of the discussion with the patient. Dr. Shuch: Got it. And is this still open? And when do you think we'll see results for this work? Dr. Grivas: Yes. The trial is still open. There is a way to go. It started accrual fairly recently, and I think their efforts for accruing patients in multiple cancer centers. So I would definitely consider this clinical trial for patients who are thinking about getting removal of the bladder and who [are well enough to] get chemotherapy, and they can discuss that option with a medical provider because the trial's going to be open at their cancer center or another cancer center. So definitely, it’s open and accruing patients. Dr. Shuch: I see. It seems very exciting that they're moving this type of therapy to a new space. Petros, keep us posted as this trial progresses. Dr. Grivas: Thank you. Will do. Dr. Shuch: So moving on to kidney cancer. Monty, let's discuss this PDIGREE trial. [Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study] Besides obviously having a very interesting name, it seems like it's a pretty novel type of approach. Can you briefly summarize the study and design? Dr. Pal: Yeah. Thanks, Brian. So the intent of this study is to take patients with advanced kidney cancer—these are folks where the cancer has [spread] beyond the borders of the kidney to the lungs, to the liver etc. All patients receive standard immune-based treatment in the upfront setting. And then a couple of months in, they actually look at the response that they've achieved, and based on that, decide on different lines of treatment beyond that. Dr. Shuch: So who is the ideal patient for this study? Who is it intended for? Dr. Pal: Yes. So this particular study, as I've mentioned, is really for those patients with advanced disease. And beyond that, we in the clinic are using different criteria [to assess] how functional a patient is. It's based on their labs, etc., to define whether or not they have what's termed good risk, intermediate risk, or poor risk. And I think as you're looking at treatment options, as a patient with kidney cancer, it's important to figure out which one of those risk criteria you fit into. This particular trial is intended for patients with intermediate and poor risk. Dr. Shuch: Got it. So these are patients that are newly diagnosed. Correct? Dr. Pal: Exactly. Exactly. Dr. Shuch: So what is the current standard of care for these patients? What would you give them outside of this trial? Dr. Pal: There's a number of options for kidney cancer. When I started in this business, we only had about 2 to 3 treatments for the disease. And now, it's expanded to more than 12 FDA-approved therapies, which is just mind-boggling. Typically, if you're just diagnosed with advanced or metastatic kidney cancer, you'll start with a combination of immune treatments, 2 immune therapies. And that's really the basis of this particular trial. Or you might get a mix of targeted treatment and immune treatment up front. Dr. Shuch: So Monty, if we have so many exciting therapies, what is the problem that the clinical trial team is trying to solve here? Dr. Pal: Great question. I think the big issue is that we know that patients who aren't doing well in therapy need to be switched. We know that patients who are doing exceptionally well on therapy can be continued on their current treatment. For the in-betweens, for patients who might have some stability in their tumors, but maybe not the type of shrinkage that we want to see, we really don't know what the best option is. And that's really where the PDIGREE trial comes into play. Dr. Shuch: So with that in mind, how is it designed to kind of answer that question? Dr. Pal: So again, we're taking patients who are receiving immune therapy in the upfront setting. We're taking a look at their response at around the 3-month mark. And typically, if you're a patient with kidney cancer, that's how often I would image you with scans. So at the 3-month mark, we look and see. If you've got a complete response—I think it's pretty intuitive—you're just going to continue on immune treatment. If you're actually having a very poor response, meaning the cancer is continuing to grow, it's migrating to new sites, you'll go on to targeted therapy. On the other hand, if you're in-between, if tumors are maybe shrinking more modestly, or just staying the same size for the most part, that's when you would be randomized to either continue on immune therapy alone, or go on a mix of targeted therapy with immune therapy. Dr. Shuch: So what is the overall question that the study is hoping to answer? The patients who are getting that additional targeted therapy, what is the hope for them? Dr. Pal: I think really what we're hoping to see is that those patients actually have delays in their cancer progression. There will be a longer time until they see their cancer grow. Furthermore, we're hoping, actually, that we might improve the survival of these patients. Dr. Shuch: Got it. So the patients who are starting this therapy, and they have an additional medication, that targeted drug, what would their specific risk be by participating in this study with that drugs? Dr. Pal: So we've had some great conversations with Dr. Agarwal around the targeted therapy in prostate cancer. He was talking about PARP inhibitors. In kidney cancer, the general principle of targeted therapies are they tend to cut off the blood supply to tumors. But they don't just do it there. They can do it in other organ systems, as well. By virtue of that, you can have a handful of different side effects, including hand-foot syndrome, which is peeling of the skin on the hands and soles of the feet. You can potentially have high blood pressure as a consequence of that mechanism. You can also have diarrhea. These tend to impact the gut. Those tend to be some of the principal side effects. But, of course, I always refer patients to the consent form for these studies for a more exhaustive review. Dr. Shuch: Got it. But some patients may not have any of these side effects. True? Dr. Pal: You're absolutely right. It's just amazing to me that I have more than a handful of patients in my practice who experience little or none of these toxicities. Having said that, it's still so important to disclose the possibilities when you're discussing these trials. Dr. Shuch: Got it. Is this trial still open to patients? And when do you think the results would be available? Dr. Pal: So at this particular trial is planning to accrue several hundred patients. And we're really in the trial's infancy. We've just had over about 150 patients accrued to date. So there's still ample opportunity to get the study for your patients in practice. And to the patients who are listening to this, it's certainly a trial that I would like you to inquire about at your respective cancer centers. It's open all over the country. Dr. Shuch: Well, Monty, that seems really fascinating. The idea that it's an adaptable trial, that patients start on therapy, and you see how they do. We'll definitely keep an eye out for that trial in the next few years. Dr. Pal: Thanks a lot, Brian. Dr. Shuch: Great. So thanks to our guests. Thank you for tuning into this podcast. I'd like to thank my guests Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta Pal. There are many types of clinical trials for urologic cancers that are ongoing, all with the shared goal of improving the way we treat these diseases. If you're wondering about participating in a clinical trial that might be right for you, definitely, talk to your healthcare provider. Please tune in next time for further discussions on additional advances in our urologic cancer field. Thank you so much. ASCO: Thank you, Drs. Shuch, Agarwal, Grivas, and Pal. Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

Topics of discussion: Q 6 week pembrolizumab dosing schedule FDA approved Updates on possible PARP inhibitor use. Niraparib for ovarian maintenance. Olaparib in prostate cancer (5:28) The monarcHER study of abemaciclib in HER+ MBC (12:20) The GRIFFIN study of Dara+VRD in myeloma (17:00)

[MUSIC PLAYING] ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Kara Nyberg. Joining me today is Dr. Emily Bergsland, who is a GI medical oncologist and professor of medicine at the University of California San Francisco. Welcome to the podcast, Dr. Bergsland. We're here to discuss highlights from the 2020 Gastrointestinal Cancer Symposium, for which you served as the program chair. Let's begin with research presented at the meeting that has a direct bearing on clinical practice. Are you and your colleagues going to change your practice based on data coming out of this symposium? And if so, how? Dr. Bergsland: There were a couple of important advances reported at the meeting that are likely to support new standards of care moving forward. We know that BRAF V600E mutated metastatic colorectal cancer is associated with a very poor prognosis. The BEACON trial was a randomized phase III study of encorafenib plus cetuximab, with or without binimetinib, in previously treated BRAF mutant metastatic colorectal cancer. The BEACON investigators had previously reported that triplet therapy seemed to be better than doublet therapy and improved survival and response rates compared to standard of care treatment. Dr. Bergsland: At ASCO GI, Dr. Kopetz presented updated results showing that encorafenib plus cetuximab, with or without binimetinib, demonstrated longer maintenance of quality of life, and there was no difference in the quality of life benefit between the doublet and triplet regiments. Furthermore, the median survival is now the same in both groups, 9.3 months, which is significantly better than the 5.9 months seen in control. As a result, the study team is moving forward with doublet therapy instead of triplet therapy, and this filing is now under review by the FDA. Dr. Bergsland: Updates to the IMbrave150 study were also reported. The IMbrave150 study was a randomized phase III trial of atezolizumab plus bevacizumab versus sorafenib as first line treatment for unresectable hepatocellular carcinoma. As reported at ESMO Asia, atezolizumab improved overall in progression-free survival compared to sorafenib. At ASCO GI, the study team reported that atezolizumab was also associated with significant and consistent benefits in quality of life, functioning, and key symptoms, providing further support for atezolizumab as a new standard of care for untreated hepatocellular carcinoma. Dr. Bergsland: Finally, the results of a randomized phase II trial of gemcitabine and cisplatin, with or without the PARP inhibitor veliparib, in patients with pancreatic cancer and germline BRCA or PALB2 mutations were presented. Surprisingly, both arms were highly active, with an overall response rate of 74% with triplet therapy and 65% with chemotherapy alone. Olaparib added little benefit, possibly because of heme toxicity limiting the dose delivered. But the high response rate and overall survival of 15 to 16 months in both groups provide support for gem/cis as a new reference treatment for pancreatic cancer in patients with germline BRCA or PALB2 mutations. ASCO Daily News: Are there any new treatment approaches or agents in development that you're particularly excited about? Dr. Bergsland: Several presentations focused on biomarkers and liquid biopsies in particular, which I think is where the field is going. The potential value of circulating tumor DNA to guide therapy was highlighted by a study presented at GI ASCO comparing tumor tissue genomic profiling to plasma circulating tumor DNA sequencing using the SCRUM-Japan GI screen and GOZILA combined analysis. Dr. Bergsland: Investigators found that plasma genotyping significantly reduced turnaround time compared to tumor tissue, 35 days versus 12 days, and led to a shorter interval between genotyping and enrollment to match trials. Dr. Bergsland: There are many prospective clinical trials incorporating circulating tumor DNA underway to validate the use of liquid biopsies to guide treatment, monitor for resistance in GI malignancies, and assess for minimal residual disease after resection, an example of the latter being the COBRA study for stage II colon cancer. Expanding on the idea of blood-based biomarkers, Brian Mulpin described development of a methylation-based cell-free DNA early multi-cancer detection test that can also predict the tissue of origin. Samples were collected as part of the circulating cell-free genome atlas in individuals with and without different cancers. Dr. Bergsland: Plasma cell-free DNA was subjected to a cross-validated targeted methylation sequencing assay, and the study included both training and validation data sets. The data suggests that a targeted methylation assay from cell-free DNA in the blood may represent a novel non-invasive way of detecting different GI cancers and identifying site of origin. Finally, another interesting finding relates to the fact that identification of the optimal duration and type of adjuvant therapy for patients with resected colon cancer remains a challenge. Dr. Bergsland: The Immunoscore, which measures immune infiltration in tumors, has emerged as a prognostic marker for patients with localized colon cancer. At ASCO GI, researchers presented an analysis of the Immunoscore in modified FOLFOX-6 treated patients enrolled in the France cohort of the idea study. The results confirm that the Immunoscore is prognostic in these patients. Interestingly, only patients with Immunoscore intermediate or high benefited from six months of FOLFOX treatment compared to three months. Dr. Bergsland: This was true in both clinical low and high risk subgroups with stage 3 disease. This means that Immunoscore low patients not only have a higher risk of relapse, but they have no obvious benefit from six months of FOLFOX compared to three months. Validation of the results in an independent cohort is planned, but the findings could represent an important step towards improving our ability to individualize adjuvant chemotherapy in patients with resected stage 3 colon cancer. ASCO Daily News: I know that immunotherapy with checkpoint inhibitors has captured much of the limelight in recent years. Were there any new and notable findings with regard to these therapies? Dr. Bergsland: Given the IMbrave150 results showing the value of atezo-bev in first line hepatocellular carcinoma, the CheckMate 040 study results are of interest. This was a study of 71 patients with advanced hepatocellular carcinoma randomized to receive nivolumab plus cabozantinib, with or without ipilimumab. Radiographic responses were seen in both groups, 19% with the doublet and 29% with the triplet, and a high disease control rate was observed in both arms. Overall survival after two years of follow-up was at least 22 months in both arms. Dr. Bergsland: The triplet regimen was associated with more toxicity. Additional studies integrating safety, efficacy, and patient reported outcomes will be needed to determine the relative value of either of these regimens compared to other treatment options for hepatocellular carcinoma. Updated CheckMate 142 data were also presented regarding the use of nivolumab plus low-dose ipilimumab as first line therapy in MSI-high metastatic colorectal cancer. Nivolumab, with or without ipilimumab, is already FDA approved for chemotherapy-resistant MSI-high metastatic colorectal cancer, but the role of combination therapy in the first line setting is unknown. Dr. Bergsland: CheckMate 142 included 45 previously untreated patients with MSI-high or defective mismatch repair metastatic colorectal cancer. At a median follow-up of 20 months, the overall response rate is 64%. The median overall survival and progression-free survival have not been reached. Combination therapy was well tolerated. This may represent a new first line treatment options for these patients, but longer follow-up is needed to see if the high response rate translates into improved overall survival. ASCO Daily News: Interesting. Let's move now to earlier stage disease. What advances were discussed related to the treatment of localized GI malignancies? Dr. Bergsland: There were several presentations focused on the treatment of localized disease, and the theme seemed to be that less may be more. In terms of surgical questions, Dr. Yamada presented preliminary results from the TOP-G trial, a randomized phase II study showing that omentum-preserving gastrectomy is associated with similar short-term outcomes compared to standard of care gastrectomy with omentectomy. The results are not definitive, but support enrollment to an ongoing phase III study, JCOG1711, which would provide a definitive answer on the role of omentectomy. Dr. Bergsland: In another randomized study, extensive peritoneal lavage did not improve survival compared to surgery alone. This is not recommended for patients undergoing curative gastrectomy for cancer. Finally, researchers from Japan reported on the results of the randomized phase III iPAC study. Primary tumor resection followed by chemotherapy did not improve overall survival compared to chemotherapy alone, thus can't be routinely recommended for colorectal cancer patients with an asymptomatic primary tumor and synchronous unresectable metastases. 87% of patients in the control arm were able to avoid surgery. Dr. Bergsland: In terms of adjuvant therapy, the RESONANCE trial assessed the use of perioperative SOX chemotherapy in patients with resectable gastric cancer in China. 772 patients were randomly assigned to receive pre- and post-op SOX or adjuvant therapy alone. Neoadjuvant SOX was associated with a higher R0 resection rate, acceptable adverse event profile, and no differences in short-term outcomes. The primary endpoint of three-year disease-free survival has not been reached, though, so this approach remains investigational. Dr. Bergsland: The results of CCOG-1302 were also presented, a randomized phase II trial assessing CAPOX with continuous versus intermittent use oxaliplatin as adjuvant chemotherapy for stage 2 and 3 colon cancer. CAPOX with planned intermittent oxaliplatin substantially reduced long-term peripheral sensory neuropathy in patients treated with six months of adjuvant therapy, and three-year disease-free survival was similar between groups. Dr. Bergsland: While intriguing, the results are not practice-changing, as it was a relatively small phase II study. Finally, the Dutch Art-Deco phase III study showed that radiation dose escalation, up to 61 gray to the primary tumor, increased toxicity without increasing local control or overall survival compared to standard dose radiation in patients with esophageal cancer receiving definitive chemoradiation. ASCO Daily News: The theme for the GI Cancer Symposium this year was accelerating personalized care. Based on research presented at the meeting, what is the field currently doing well, and what can the field be doing better? Dr. Bergsland: Generally speaking, I think we're making significant progress. One big area of study relates to identification of patients at risk for GI malignancies and modifying cancer screening guidelines accordingly. For example, there was a session on screening in high risk populations. Providers should offer germline testing to any patient with a personal history of pancreatic cancer, since approximately 10% of patients will have an inherited germline mutation. Dr. Bergsland: Guidelines for screening continue to evolve, but their emerging data support the use of MRI or EUS in mutation carriers. Cholangiocarcinoma rates are increasing globally, and we know that the risk factors vary by location and that type 2 diabetes, a non-alcoholic steatohepatitis, or NASH, may also be contributing. NASH cirrhosis is also a risk factor for hepatocellular carcinoma. Screening practices are evolving as our recommendations for chemo prevention, which may include aspirin and statins in high risk patients. Dr. Bergsland: Another important area is early onset colon cancer. Colorectal cancer incidence has been declining for several decades in people over the age of 55, but rates in people younger than 55 are increasing at nearly 2% annually, and this has been ongoing since 2006. Younger patients present with more advanced disease and more poorly differentiated tumors. As such, there's an ongoing debate surrounding the optimal age to start screening. Better colorectal cancer risk prediction tools are needed. In the meantime, high risk groups should be prioritized, such as those with a family history of cancer, inflammatory bowel disease, or polyps. Dr. Bergsland: In addition to improvements in our identification of high risk patients, we're also making great strides in translating advances in our understanding of the molecular underpinnings of GI malignancies to the clinic. The BEACON data are certainly encouraging with respect to the treatment of BRAF V600E metastatic colorectal cancer, and the molecular basis for cholangiocarcinoma is now much better understood, with biomarker-based trials now available for FGFR and IDH-mutant cancers. Despite the many advances presented at the meeting, though, there were a few disappointments, suggesting that there's still a lot of work to be done in the area of biomarker selection and drug development. Dr. Bergsland: The HALO-109-301 study of nab-paclitaxel/gemcitabine, with or without PEGPH20 in patients with previously untreated hyaluron-high metastatic pancreatic ductal adenocarcinoma was a negative study in a biomarker-selected population. There were also several negative studies in biomarker-unselected patients. The SEQUOIA study of FOLFOX with or without pegylated interleukin-10 as second line therapy for metastatic pancreatic cancer was negative, and there was no benefit in adding ramucirumab, a VEGFR-2 antibody, or merestinib, an oral MET inhibitor, to gem/cis and biomarker on selected metastatic biliary cancer. Dr. Bergsland: Finally, Australian researchers reported results from the Christoral NET study. Adding chemotherapy to lutetium-177 dotatate in mid-gut neuroendocrine tumors added toxicity without improving efficacy. The results of these studies highlight the ongoing need to identify validated biomarkers that facilitate drug development. This trend is reflected in our clinical trials, with biomarker selected patient populations using tumor-based biomarkers, germline alterations, or circulating tumor DNA increasingly under study. Dr. Bergsland: Adaptive platform trial designs, such as the platform study of maintenance therapy in gastroesophageal cancer and PanCAN's Precision Promise clinical trial in the first line and second line treatment of metastatic pancreatic cancer, are being incorporated to more efficiently test new therapies by requiring fewer patients to understand if a potential therapy is working and support the testing of multiple investigational therapy simultaneously. ASCO Daily News: To take things one step farther, how are we doing in terms of actually delivering personalized cancer care? Are we making improvements in patient access to treatment and follow-up? Dr. Bergsland: The available data suggests we have a long way to go in terms of ensuring equitable access to care across all patients. Disparities in health care delivery were highlighted in several presentations. An analysis of NCDB data revealed that young adults with colorectal cancer in the lowest income and education population had worse overall survival. And regardless of income, patients in metropolitan areas have a lower risk of death, presumably due to greater access to care. Another group analyzed health care in Canada and determined that 1/3 of patients with non-curative gastroesophageal cancer never see a medical oncologist, and only 1/3 of patients receive chemotherapy. Dr. Bergsland: Care delivery and overall survival showed high geographic variability, with location of residents influencing access to care and overall survival and inferior outcomes for those living further from a cancer center. Dr. Yousef Zafar gave a keynote lecture focused on how advances in precision oncology can be realized equitably across all patient populations, communities, and health care systems. He reminded us that in 2017, only 60% of patients with metastatic colorectal cancer were getting appropriate molecular testing. He also reviewed the costs of cancer care and the impact financial toxicity has on patients. Dr. Bergsland: Dr. Zafar outlined a need for what he calls "precision delivery of care," which, to be successful, will require collaboration between drug manufacturers, insurance providers, health care providers, and patients, and discussions of clinical benefit toxicity and cost. In the era of precision oncology, novel methods for assessing the value of new drugs are needed, as our reimbursement models that incorporate cost effectiveness. Dr. Zafar stressed that all stakeholders will need to collaborate to find solutions that ensure precision delivery of molecular and immunotherapies to all patients. ASCO Daily News: Did we learn anything new or unexpected about the pathobiology of GI malignancies at this year's meeting? Dr. Bergsland: I think one of the most interesting sessions at the meeting was a keynote lecture given by Susan Bullman, a scientist at the Fred Hutchinson Cancer Research Institute. Dr. Bowman reviewed the importance of a microbiome in the human body and in disease. She explained that the naturally occurring microbes in our bodies may confer susceptibility to certain cancers, promote cancer progression, and modulate response to therapeutics. Dr. Bergsland: For example, tumor associated bacteria are metabolically active and can potentially increase or decrease the activity of certain chemotherapeutic agents, such as gemcitabine. In addition, there is a growing body of evidence that tumor microbiome may modulate the response to immunotherapy. Dr. Bullman's presentation highlighted this exciting new area of study as well as the many unanswered questions in the field, including whether the tumor microbiome itself might be a valid target for cancer therapy. Studies of the microbiome in colon cancer and other diseases are ongoing. ASCO Daily News: I agree, that was a very fascinating keynote lecture. Given the legalization of marijuana in an increasing number of states, an entire session at the symposium was dedicated to symptom management in the era of legalized marijuana and the opioid crisis. What notable points came out of that session? Dr. Bergsland: There is great interest in the use of cannabinoids in the face of increased access and legalization in a number of states in the US. The data suggests that patients prefer information about safety and efficacy from their health care providers, but many providers cite inadequate training in this area. Our understanding of the role of these agents is limited by a lack of prospective clinical trials. The strongest evidence for efficacy is in the area of the control of chemotherapy-induced nausea, but it's unclear if cannabinoids impact tumor growth, as most of the studies in this area have been preclinical. Dr. Bergsland: In terms of practical treatment considerations in the absence of high quality data on strain, dosing, ratios, and potencies of active ingredients and modes of use, a harm reduction model of care is recommended starting with very low doses, with THC-CBD combinations preferred over THC only preparations. Definitive recommendations are further complicated by the lack of information about drug-drug interactions and limited information about quality control. Overall, the panel felt that cannabinoids were not likely to ever replace opioids, so prescribers still need to know how to use opioids in the clinic, keeping an eye out for patients with risk for abuse of these agents and remembering to incorporate a bowel regimen as well as an antiemetic in the first few days. ASCO Daily News: This was truly an excellent recap. I think we can summarize by saying there was a wealth of research that was presented at the GI Cancer Symposium this year, both positive and negative, that's moving the field forward. It's been a pleasure speaking with you, Dr. Bergsland. Thank you for your time and your insight. To our listeners, thank you for tuning into the ASCO Daily News Podcast. If you are enjoying the content, we encourage you to rate us and review us on Apple Podcast. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.     [MUSIC PLAYING]  

This week we're treating you to a recording of the Grand Rounds lecture on overdiagnosis and cancer screening that Dr. H Gilbert Welch gave at Oregon Health & Science University on October 30, 2019. Before the lecture, we take a moment to reiterate with renewed vigor our distaste for the POLO trial (first discussed in episode 1.64). POLO: doi.org/10.1056/NEJMoa1903387 Back us on Patreon! www.patreon.com/plenarysession

[music] ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. The European Society for Medical Oncology 2019 Congress was held in Barcelona, Spain, from September 27 to October 1. In this podcast, Dr. Ricardo Cubedo shares highlights from the meeting, including treatment advances in ovarian and lung cancer. He also discusses a new type of clinical trial known as “basket trials” and the ways they are changing the shape of cancer research. Dr. Cubedo is the Head of Sarcomas and Hereditary Cancer with the Medical Oncology Service at MD Anderson Cancer Center Madrid. He is also a member of the Cancer.Net Editorial Board. ASCO would like to thank Dr. Cubedo for discussing this research. Dr. Ricardo Cubedo: Good day, everybody. My name is Dr. Ricardo Cubedo. I am a medical oncologist from Madrid, Spain, from MD Anderson Cancer Center Madrid, and I was among the 25,000 attendees coming from all around the world, attending the last European Society for Medical Oncology Meeting, which took place between 27 September and 1st of October in Barcelona, which is a very beautiful Spanish city by the Mediterranean sea. We had a record-breaking 3,900 scientific communications, so you can bet that there is a lot to choose from, but I have chosen for you 3 topics. Two of them are relevant on their own, and very important results, and the last 1 I think it goes beyond the results themselves, changing the way we figure out things in order to fight cancer. The first item is the results of the PAOLA-1 trial, focused on advanced ovarian cancer patients. You know that ovarian cancer is the most lethal gynecological cancers, because we cannot cure it when it is diagnosed too late to remove it, usually because it is too widespread within the belly. Nowadays, those patients rely on chemotherapy in order to stop the disease, control their symptoms, and live longer. We usually use chemotherapeutics based on platinum as front-line treatment, which are just too toxic to use all the time. So the way we do it, we give the chemotherapy for some months, then stop, then used again when the disease starts progressing and the patient becomes symptomatic. Those months between one chemo period and the next one, are precious for ovarian cancer patients, because they can enjoy them free from both the burden of progressing disease and the side effects of platinum chemotherapy. The new drug that was the center of the PAOLA-1 trial is called olaparib. It is a new non-chemotherapy drug that targets directly the DNA of the tumor cells. And what it does is to prevent the DNA in the tumor cell from repairing itself when it is damaged, and that ultimately leads to the death of the tumor cell. What PAOLA-1 researchers really wanted to know is if olaparib, the new drug, was useful to delay progression once the disease was already stabilized by chemotherapy, giving patients a longer period free from chemo between 1 treatment and the next 1. That seemed a good idea, because olaparib is given as pills and has few side effects. 800, more or less, ovarian cancer patients were recruited into the trial from several countries all across Europe and were divided into 2 groups. Group number 1 were treated in the standard fashion: that is, chemotherapy until the tumor stopped, and then, maintenance with a drug called bevacizumab, which already been proven to delay the need for further chemotherapy. That is the standard. In the group B, the second group, that was the experimental group, olaparib, the new drug, was used on top of the standard treatment. Once the disease was [ceased?] with chemotherapy, patients were put on olaparib, and the results were impressive. In the control group, the median time that the cancer took to reactivate was 16 months, one-six, but the group of women treated with Olaparib didn’t need further chemotherapy for a period just shy of 2 years. Researchers even spotted a group of patients with certain mutations in the tumor DNA that achieved an astounding 37-month progression-free survival. Being able to delay a new period of chemotherapy for over 3 years is a big, big improvement for women with advanced ovarian cancer, and a very welcome new tool in our weaponry against the disease. That was the first item I wanted to discuss with you. The second one is also a clinical trial, a big clinical trial, called CheckMate 227. You know, we oncologists like to give trials those funny names. This is a trial for lung cancer patients. It is a very large study. It is still ongoing in over 300 hospitals all over the world, also in America. The non-small cell variety of lung cancer is the most common subtype of the disease and a really ruthless one. Lung cancer kills, every year, more Europeans or Americans than any other malignant tumor. So it’s no wonder that huge resources are devoted to research against this beast. Being such an aggressive disease, equally aggressive chemotherapy has been the cornerstone of its treatment, when the tumor has grown or spread beyond the reach of surgery. Again, the problem is that such overaggressive treatments like combination chemotherapy with 2 or 3 drugs at the same time, might put a temporary break on the disease but unfortunately at the expense of quality of life. What the CheckMate 227 trial explores is the role of immunotherapy. Immunotherapy, I am sure you have heard about it, is a new field of anticancer drugs, non-chemotherapy drugs, that do not attack cancer cell themselves but, instead, use some kind of molecular trickery to shake our own immune system against the tumor. The combination of 2 of such immunotherapeutic drugs, which are called nivolumab and ipilimumab, was compared in this trial to standard chemotherapy. So 1 group received the usual chemotherapy, and the other group received no chemotherapy at all, but those 2 immunotherapeutic agents combined. The results were eagerly awaited, probably the most expected results in the whole meeting, and were disclosed in Barcelona amidst much expectation at a fully packed hangar-sized conference room. The full size of the trial is suspected to be north of 2,000 individuals, but we already know what happened to the first 800 group of patients during a 2-year period, and the results are quite encouraging. Unfortunately, non-small cell lung cancer is still a deadly disease, because no matter which treatment patients received within the trial, less than half of them were still alive at the 2-year mark. But while only one-third of the patients treated with current state-of-the-art chemotherapy were alive 2 years after treatment, 40% reached the 2-year bar among those treated with immunotherapy. Moreover, and more importantly, there were hints of a small group within that 40%, approximately 2 out of every 10 patients, that stabilized for long periods of time. Something very similar, stabilization, was observed some years ago, when we started to use immunotherapy in melanoma patients. And we now know that many of those patients, stabilizing for many years, are now in fact cured, even with extensive metastasis widespread into many organs. So at first glance, CheckMate 227 results might not seem much, but they mean that, for the first time, we have proved we can treat advanced lung cancer patients without a single drop of chemotherapy, which means much better quality of life. And we have, also for the first time, a realistic prospect for a cure, more beyond mere wishful thinking. So we have seen the results of a couple of trials which are what we call “practice changing,” which means that many ovarian or lung cancer patients worldwide, should be treated in a different way, with better results, as soon as their oncologists attending the meeting fly back to their working sites. Lastly, the third piece of information I would like to share with you proves we are now right in the middle of a medical revolution. It’s not surprising if I tell you that the first thing an oncologist like me will try to figure out when faced with a new advanced cancer case is where it comes from, because we do not equally treat a breast cancer case, a stomach cancer, or lung cancer. Well, it has been so until recently. During the last decade we have learnt quite a bit about the nuts and bolts of cancer. Specific gene mutations and wrecked proteins are both the hallmarks of cancer cells and targets for new drugs. I will give you an example: several years ago researchers found a protein called HER2 on the surface of cancer cells in 2 or 3 out of every 10 breast cancer patients. What this protein does is to rev up the cell’s machinery keeping it in constant multiplication and leading to fast tumor growth, so those were patients with very bad prognosis, as the tumor that grows rapidly, also spreads rapidly. But a new drug called trastuzumab was tailored to disable HER2, the protein that was accelerating the tumor cell, and that made a huge leap in the treatment of HER2-positive breast cancer patients. But the white-coated guys at the research labs showed us that HER2 was not only present in breast cancer, but also in subsets of gastric, lung, ovary, womb, bladder, colon, and head and neck tumors, which was quite surprising, because those are completely unrelated malignancies. Nowadays, trastuzumab, the breast cancer drug, is also used to treat gastric tumors and is beginning to raise interest in the lung cancer arena too. Well, inspired by those facts, some brave oncologists began to think out of the box and wondered if all we really need to know is the mutations and other molecular characteristics of the tumors in order to select treatments targeted against them, no matter where the cancer comes from. To treat in the same way, a colon cancer, a thyroid cancer, a breast cancer, or a brain cancer, provided they have the same molecular basis. Well such ideas were so revolutionary, they raised a few eyebrows and a lot of skepticism, but, well, this is science and we do not dismiss ideas without some previous research. Thus, the so-called “basket trials” were designed and carried out. Patients in such “basket trials” were hand-picked based on specific mutations and put to treatment, just like one chooses ripe berries and collects them into the basket. The result of such ground-breaking trials proved that the concept was right. In this Barcelona meeting, Dr. Christian Dittrich from Vienna presented us with the combined results of 2 basket studies: the SCOUT and the NAVIGATE trials. Both explore the activity of a new drug called larotrectinib, in patients with any kind of cancer, provided their tumors had a mutant form of a protein called TRK. When healthy, TRK proteins are essential for a healthy brain and nervous system. But once mutated, TRK leads to cancer in several organs. And that was the basis of the trial. The new drug, larotrectinib, is carefully designed to disable the mutated TRK proteins while sparing the healthy ones you need. Both clinical trials combined included, more or less 160 patients, from children under 1 year to 84 year old adults. The results presented at the meeting in Barcelona were rewarded with the general applause from the audience, because they were astounding. 80% of the patients responded to the drug, more than thee-quarters of them still without signs of any health deterioration 1 year after they were given their first dose. Such results are really remarkable, as we are speaking of a group of patients diagnosed with no less than 18 different types of cancer, treated with a single drug, many of them having failed to several previous treatments or resistant to any known therapy. Those results are not practice changing, because we have to resolve a lot of questions first, but are very exciting because they open a new drug for cancer treatment. After a good medical meeting you go back home with some answers. But after a really good one you collect many more questions than answers. Are we going to treat patients based on their tumor genetics instead on classical tumor types? How are new treatments to be combined? Which ones should be given frontline, which ones after progression? What genes should be checked in tumor biopsies on a routine basis? Are there late side effects still to be seen from the new drugs? When to stop maintenance treatments? Are some long-lasting responders really cured of their cancer? How are we going to pay for the new ultra-expensive fancy drugs, some of which are to be maintained for years, even lifelong? Many, many questions to answer. One thing I assure you: these are thrilling times to be an oncologist. I thank you all for your attention. ASCO: Thank you, Dr. Cubedo. Listen to more research highlights from scientific meetings: subscribe to Cancer.Net Podcasts on Apple Podcasts or Google Play, or visit www.cancer.net. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support. [music]

La Dra. Nora Sobrevilla nos resume lo más importante del estudio PROfound, donde se compara olaparib vs enzalutamida o abiraterona en CPRCm.

The present podcast gives a short summary of the PAOLA-1 trial investigating the addition of Olaparib to bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer treated with platinum-based chemotherapy plus bevacizumab. Expert: Isabelle L. Ray-Coquard Affiliation: Centre Leon Bèrard, Université Claude Bernard Lyon, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire (GINECO), Lyon, France

El Dr. Iván Coto nos habla sobre el diseño de estudio y resultados del estudio POLO

MUNICH—The role of poly ADP ribose polymerase (PARP) inhibitors for treating newly diagnosed advanced ovarian cancer was under review at the 2018 annual congress of the European Society for Medical Oncology (ESMO) in the light of findings from the SOLO1 …Jonathan Ledermann AJO

BRCA1/2 Ovarian Cancer—Three Years Disease Free with First-Line Olaparib MUNICH—An “unprecedented improvement” in progression free survival (PFS) was observed in the randomized controlled double-blind phase three SOLO1 study of women with newly diagnosed ovarian cancer who had BRCA1/2 mutations and …Kathleen Moore OLAPARIB FIRST LINE IN OVAIAN CANCER

FDA medical oncologists discuss the January 12, 2018, approval of olaparib, the first PARP inhibitor approved for the treatment of patients with metastatic breast cancer with a germline BRCA mutation.

Dr. Linh Alejandro, a clinical oncology pharmacist at the University of California, San Diego Health Systems discusses the approval of olaparib for germline BRCA-mutated metastatic breast cancer.

Dr Bang speaks with ecancer at ESMO 2016 to discuss outcomes of the GOLD trial, combining olaparib and paclitaxel to treat advanced gastric cancer. Compared to paclitaxel alone, olaparib extended overall survival and progression free survival, but did not reach a p value indicating statistical significance. While the trial is negative, Dr Bang describes the outcomes of indicative of a role for olaparib in future studies.

Dr Farago speaks with ecancer at AACR 2017 about results from a phase I/II study of treating patients with small cell lung cancer (SCLC) following relapsed after chemotherapy. She describes the rationale of adding olaparib, a PARP inhibitor preventing DNA repair, to temozolomide which induces single strand breaks, with a hopeful synergy for controllable cell death within tumours. Dr Farago describes the doses in the trial as well tolerated, with a response rate of 48% and a median PFS of 5.6 months. She also highlights the utility of patient derived xenografts to chart patient responses through time, and identify stages of resistance and response.

Dr Robson presents, at a press conference at ASCO 2017, findings from a phase III clinical trial of around 300 women that may introduce PARP inhibitors as a new type of treatment for breast cancer.

Dr Robson speaks with ecancer at ASCO 2017 about the growth-limiting application of olaparib, a PARP inhibitor, to treat BRCA breast cancer. He describes how, among 300 women included in the trial, disease progression was slowed by up to 3 months, reducing the chance of disease progression by 42%.

Prof Ledermann talks to ecancertv at ASCO 2016 about the updated survival data associated with the PARP inhibitor olaparib in a certain subset of ovarian cancer patients. He also highlights the novel exploratory endpoints that were used for the first time within an oncology trial (TFST and TSST), and highlights that 15% of patients entered into the study possessing mutant strains of BRCA are still receiving maintenance therapy 5 years later. For future clinical use, it is important to establish precisely those patients who will benefit the most, due to the cost of the drug.

Dr Liu talks to ecancertv at ASCO 2014 about the findings from a federally funded, NCI-sponsored phase II study which suggest that the combination of two investigational oral drugs, the PARP inhibitor olaparib and the anti-angiogenesis drug cediranib, is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes than olaparib alone.

Today in FirstWord:

Today in FirstWord:

WORD of HOPE Ovarian Cancer Podcast. Episode 02, Topic 2 of 10.This is the second episode in the series of "10 Exciting Ovarian Research Topics from 2010". This episode focuses on PARP Inhibitors. Be sure to look for the remaining topics of this series in subsequent episodes of WORD of HOPE Ovarian Cancer Podcast.For show notes, links, info, and how to subscribe, visit: www.wordofhopepodcast.com