POPULARITY
Dr. Angela DeMichele, Dr. Lynn Henry, and Dr. Harold Burstein present the latest breast cancer rapid recommendation update impacting two ASCO guidelines. This update focuses on the new option, capivasertib plus fulvestrant, for patients with hormone receptor-positive, HER2-negative metastatic breast cancer with activating PIK3CA or AKT1 mutations or inactivating alterations in PTEN based on data from the recent CAPItello-291 trial. They discuss the updated recommendations on lines of endocrine treatment and selecting between the options for patients with activating PIK3CA mutations. Additionally, we discuss implications for clinicians and patients, and what ongoing research is occurring in the field. Read the latest update, “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer – Capivasertib-Fulvestrant: ASCO Rapid Guideline Update“ at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00248 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute, Dr. Angela DeMichele from the University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, co-chairs on “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Capivasertib–Fulvestrant: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Burstein, Dr. DeMichele, and Dr. Henry. Dr. Harold Burstein: We're happy to be here. Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes. So then, to kick us off, Dr. Burstein, could you first describe what prompted this rapid update, which provides updated recommendations for two ASCO guidelines: the biomarkers for systemic therapy in metastatic breast cancer guideline, and the endocrine treatment and targeted therapy for hormone receptor-positive, HER2-negative metastatic breast cancer guideline? Dr. Harold Burstein: Thanks, Brittany. Well, this team has been working, as you mentioned, actually, on two guidelines, which are clearly evolving in parallel and kind of converging, actually, when you look at data, as we'll be talking about in the next few minutes. The particular catalyst here was a large randomized clinical trial which looked at a new targeted therapy in the space of estrogen receptor-positive, HER2-negative breast cancer. That drug is capivasertib. And the trial was the so-called CAPItello study. In that trial, patients who were receiving second-line therapy with fulvestrant were randomized to that treatment alone, or that plus capivasertib. So the data from that study were the first strong signal that we needed to update the guideline because they were important clinical data. The other strong signal was that the drug was tested in a cohort of patients who had a specific set of mutations in their cancers. And that included PIK3CA mutations, a class of mutations for which we already had a targeted drug. But it also included some new potential targets, including mutations in the AKT gene itself, capivasertib is an AKT inhibitor, as well as loss of PTEN protein functionality, which potentially sensitizes tumors to the targeted action of this drug as well. So while we had a couple of guidelines catching up on the endocrine therapy space, which is increasingly looking like a targeted therapy space, it was clear that this major study, which had clinical and diagnostic implications, would sort of push them together and served as the impetus for updating both guidelines at the same time. Brittany Harvey: Understood. I appreciate that background information. So then, Dr. DeMichele, based on this updated data that Dr. Burstein just described, what is the updated recommendation from the guideline panel regarding lines of endocrine treatment? Dr. Angela DeMichele: Well, I think this is where the biomarker evolution that Dr. Burstein just referred to really comes in because now we have the opportunity to perform genomic testing in patients who have ER-positive, HER2-negative metastatic breast cancer, on either the tumor or commonly from the blood. And we can now start to tailor treatment to the specific genomic abnormalities that that patient's tumor contains. So now our guideline really marries both the genomic abnormality with the therapeutic option. First-line treatment remains endocrine therapy plus a CDK 4/6 inhibitor. But things then really start to diverge once we enter second and third-line therapy because at that point, we now have the option to test for several genomic markers: ESR1 mutations, PIK3CA mutations, AKT1 mutations, and PTEN inactivation. And based on whether the tumor has one or any of those mutations, we can then select the therapy based on that. So in the case of capivasertib, as you just heard, that is a therapy for patients whose tumors have PIK3CA mutations or activating mutations in AKT1 or loss of PTEN. But other patients who don't have one of those mutations may, in the second line, go on to another drug. For example, if they have an ESR1 mutation, they then may be eligible to take elacestrant. Patients who have no targetable mutations still have a targeted option in that they can use everolimus. And in all of these settings, the endocrine therapy partner for this line of therapy is typically fulvestrant. So now we're really starting to tailor therapy in the second- and third-line based on genomic changes. Brittany Harvey: Excellent. That information is helpful for choosing optimal therapy tailored to the individual patients, as you just described. So then, Dr. Henry, what guidance does the expert panel provide regarding choosing a PIK3CA targeted option? Dr. Lynn Henry: Thank you. So for patients whose tumors are found to have an activating mutation in PIK3CA, we now have two drug options: either alpelisib or capivasertib in combination with fulvestrant. And the problem is, these drugs have not been compared head-to-head. We can't say that one is clearly better than the other, either in terms of efficacy or in terms of side effect profile. What we do have is information from two separate trials in which they were each tested against placebo. The efficacy appears to be fairly similar based on the data that we have. It does appear that the side effect profiles may be slightly different. And so, when you have a patient sitting in front of you and you're trying to decide how best to treat her, you really have to think about, what symptoms does my patient already have? What is she more or less likely to tolerate? So what we do know is that it appears that the rates of grade 3 diarrhea and rash were slightly higher with capivasertib. It looks like hyperglycemia was higher with alpelisib, as was treatment discontinuation. So really you have to make an individualized decision when you have a patient sitting in front of you about which drug you'd like to try. Of course, if someone doesn't tolerate one drug, you can always switch to the other one. Brittany Harvey: I appreciate that analysis and to provide guidance without a head-to-head trial and to specifically provide options based on an individual patient's profile. So then, Dr. DeMichele, what should clinicians know as they implement these new recommendations? Dr. Angela DeMichele: Well, first of all, I think most clinicians now are becoming more familiar with the procedures required for doing genomic testing. But this is something that now has become the standard of care. And so, it is incumbent upon all of us who treat these patients to understand what the options for genomic testing are for that patient, which companies offer this testing, how to send a sample, and how to interpret the report that comes back. So, I think this has really added a level of complexity to the therapy for patients. I also think that one can't simply apply an algorithm to a patient. We have to really treat the whole patient and we have to take into consideration, as Dr. Henry said, the toxicities of these agents and the cost which is also a major issue. So I think that while it is more complex, really that doctor-patient relationship is so important in communicating what these genomic tests mean for a patient and for their options, and also important for the clinician to really understand what the different therapeutic agents might mean for a patient, and really try to pick the agent that's best for that patient. Using genomic testing is just one of several different features that they'll consider. Brittany Harvey: Absolutely. It's key to obtain the data needed to select appropriate patients and to recognize the complexity. So then, Dr. Henry, in your view, how will this update impact patients with metastatic breast cancer? Dr. Lynn Henry: Yes, so as we've discussed, I think this is really exciting. Over the last few years, we have had quite a number of new medications that have become available for patients and have been FDA-approved. And so this is yet the latest in a series. For those patients whose tumors have a PIK3CA mutation, as we discussed, there are now two options. So you have a choice depending on which one is better covered by insurance, by which one you may tolerate better. But I think the other thing is now, although it's a smaller subset of patients, there are patients out there whose tumors have mutations in AKT1 or alterations in PTEN, and so there's an entirely new endocrine therapy-based option available for them that wasn't available before. So I think that thinking about the new data that are out there, the new drugs that are out there, really is exciting because there are new options available and hopefully there are more to come as well. Brittany Harvey: Absolutely. It's great to have these new options. So, finally, Dr. Burstein, Dr. Henry just mentioned what's to come. Could you touch on what some of the outstanding questions are regarding endocrine therapy for patients with metastatic breast cancer? Dr. Harold Burstein: A couple of things to say. First, ER-positive metastatic breast cancer is the most common kind of metastatic breast cancer, roughly three quarters of metastatic cases of breast cancer will be hormone receptor-positive cancers. So this is a very big public health issue around the world, actually, breast cancer being the number one most commonly diagnosed cancer of women around the world. So minor or major improvements in treatment for advanced ER-positive breast cancer really have a tremendous impact. The second thing is it's been remarkable to see the progress in the past decade. We've gone from simply targeting the hormonal access itself with medicines like tamoxifen or aromatase inhibitors or an injectable selective estrogen receptor degrader like fulvestrant to incorporating targeted therapies at the same time. And this whole class of drugs called CDK4/6 inhibitors has emerged which we use in either first- or in second-line therapy. Those drugs have transformed our standard of care, improved survival for patients with advanced ER-positive disease, now with median survival nearly 50% longer than what we had seen in the past. And if you've heard, we have a wealth of opportunities. We can target PIK3CA, we can target ESR1 mutations. Other drugs emerging in the space include PROTACs which is another way of degrading the estrogen receptor. And so there's going to be more progress in the years to come. So one of the biggest challenges has been to try and understand, is there really an optimal way to use these drugs, or can we be smarter about the particular sequence of all these particular things that are happening. So one example of this was a recent study that is on a drug, not as yet FDA-approved, called inavolisib, which is a PIK3CA targeted drug used in first line in combination with a CDK4/6 inhibitor and endocrine therapy. And that study, for a high-risk group of women with ER-positive metastatic disease, actually showed a dramatic improvement in overall survival, asking the question if combining some of these targeted therapies together might yet further improve outcomes. And as you've heard from the diagnostic space, one of the other interesting things is that tumors evolve over time. And so acquisition of the estrogen receptor mutations, ESR1 mutations, which are typically not found early in the course of advanced breast cancer but otherwise later, now have targeted treatments. So there's a whole bunch of stuff going on all at the same time, including multiple ways of targeting things, serial testing to look for acquisition of ESR1 mutations and new pathways to explore. It's an embarrassment of riches in some respects because it has meant it's actually really hard to write a guideline as you've heard, which says, “Do this first, do this second, and do this third.” I suppose that's a good problem to have under the circumstances, but it's going to require really thoughtful clinical trials and careful analysis to help guide specific lines of treatment recommendations like that. Brittany Harvey: Excellent. We'll look forward to these exciting, continuing developments for patients with metastatic breast cancer. And I want to thank you all so much for your work to develop this rapid recommendation update for these two guidelines. And thank you for taking the time on this podcast today. Dr. Harold Burstein: Thanks. Dr. Lynn Henry: Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this episode, Josh interviews Dr Harold Burstein. A graduate of Harvard University and Harvard Medical School, Dr Burstein's initial PhD was in cellular immunology. After receiving his oncology fellowship at the Dana Farber Cancer Institute, he joined the staff in 1999. Hal has a particular interest in breast cancer and has participated in national and international clinical trials while also working to develop treatment guidelines worldwide. A passionate educator, Dr. Burstein teaches medical students, residents and fellows at Harvard Medical School and the Dana Farber Cancer Institute.The Kinghorn Cancer Centre and The Beverley Alt Scholarship proudly support this mini-series.The Kinghorn Cancer Centre: https://tkcc.org.au/Dana Farber Cancer Institute: https://www.dana-farber.org/For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Minor edits have been made to the episode to improve sound quality and flow. Hosted on Acast. See acast.com/privacy for more information.
In discussion with Dr. Harold Burstein, we cover treatment algorithm of HER2+ breast cancer. We covered the current standard of care treatment options for HER2+ breast cancer. #HER2 #Sensitive #Breast #Cancer #2024 #oncology #oncbrothers Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Harold (Hal) Burstein is an internationally renowned breast cancer expert. In this episode, Hal discusses a broad range of topics related to breast cancer, starting with the intricacies of breast anatomy and the endocrinological factors at play. He covers the spectrum of breast cancer, from precancerous lesions to invasive breast cancer, classifying these conditions into a helpful framework. He delves into various screening methods, including self-exams, mammograms, ultrasounds, and MRIs, and addresses the ongoing debate surrounding early screening and detection. Hal provides insights into the latest advancements in cancer treatment, offering valuable guidance for individuals to understand their unique circumstances within the three primary categories of breast cancer. Finally, Hal delves into the role of genetics in breast cancer and brings attention to the less commonly addressed issue of male breast cancer. We discuss: The prevalence and mortality rate of breast cancer in women [4:15]; The anatomy of the breast and the complex factors behind breast cancer development [6:30]; The three main categories of breast cancer [16:45]; Breast cancer risk: the impact of menopause, estrogen, breast density, obesity, and more [21:15]; Finding and evaluating lumps in the breast [25:30]; Identifying and treating precancerous lesions like ductal carcinoma in situ (DCIS) [31:00]; Post-lumpectomy for DCIS: standard of care, future risk of cancer, and pros and cons of radiation and other preventative options [41:15]; Lobular carcinoma in situ (LCIS): how it differs from DCIS in terms of treatment and future risk of invasive cancer [55:00]; Breast cancer screening: mammography, ultrasound, MRI, and more [1:03:45]; Invasive breast cancer: pathology report, surgery, and survival [1:11:00]; The argument for aggressive screening for breast cancer [1:22:15]; Advances in the treatment of breast cancer, adjuvant therapy, and neoadjuvant therapy [1:27:00]; The use of hormone replacement therapy in women who are in remission from breast cancer [1:41:15]; The role of genetics in breast cancer [1:44:45]; The importance of multidisciplinary care delivered by cancer centers [1:53:15]; Breast cancer in men [2:03:30]; Parting thoughts and takeaways [2:05:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) ER-Positive Breast Cancer — Dr Burstein (3:57) Clinical Questions and Cases (16:47) Selection and Sequencing of Treatment for Relapsed ER-Positive Metastatic Breast Cancer — Dr Jhaveri (33:32) Clinical Questions and Cases (46:02) CME information and select publications
Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Role of Hormonal Therapy in Prostate Cancer Management — Dr Smith (1:50) Clinical Questions and Cases (13:18) Evidence-Based Use of Other Therapeutic Approaches in Metastatic Castration-Resistant Prostate Cancer — Dr Morgans (26:08) Clinical Questions and Cases (38:01) CME information and select publications
Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Non-Small Cell Lung Cancer Targeted Therapy — Dr Riely (4:09) Non-Small Cell Lung Cancer: Immunotherapeutic and Other Novel Strategies — Dr Wakelee (32:23) CME information and select publications
Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Gastroesophageal Cancers — Dr Philip (1:42) Colorectal Cancer — Dr Bekaii-Saab (32:56) CME information and select publications
Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Chronic Lymphocytic Leukemia (CLL): Considerations for Front-Line Treatment — Dr Kahl (1:48) Treatment of Relapsed/Refractory CLL; Novel and Investigational Strategies — Dr Chanan-Khan (35:38) Clinical Questions and Cases (49:58) CME information and select publications
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and the South Carolina Oncology Society, featuring key clinical presentations and papers in breast cancer, gastrointestinal cancers, genitourinary cancers, chronic lymphocytic leukemia and lymphomas, gynecologic cancers and lung cancer. Featuring perspectives from Drs Tanios Bekaii-Saab, Michael Birrer, Danielle Brander, Harold Burstein, Ibiayi Dagogo-Jack, Virginia Kaklamani, Stephen Liu, Ursula Matulonis, Rutika Mehta, Craig Moskowitz, Daniel Petrylak and Sandy Srinivas.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Proceedings from a daylong multitumor educational symposium in partnership with the American Oncology Network, including key clinical presentations and papers in breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Neeraj Agarwal, Harold Burstein, Ibiayi Dagogo-Jack, Rafael Fonseca, Brad Kahl, Rutika Mehta, Craig Moskowitz, Joyce O'Shaughnessy, Krina Patel, Philip Philip, Suresh Ramalingam and Sandy Srinvas, moderated by Dr Neil Love.
Featuring perspectives from Dr Harold Burstein and Prof Peter Schmid, moderated by Dr Neil Love.
Featuring perspectives from Dr Harold Burstein and Prof Peter Schmid, including the following topics: HER2-Positive Breast Cancer Introduction (0:00) DESTINY-Breast03 (3:47) HER2CLIMB (20:46) Triple-Negative Breast Cancer OlympiA, NEOTALA (22:59) KEYNOTE-522 (32:08) ASCENT (41:23) ER-Positive Breast Cancer RxPONDER (46:22) monarchE (52:30) EMERALD (58:18) SOLAR-1 (59:52) CME information and select publications
An interview with Dr. Harold Burstein from Dana Farber Cancer Institute in Boston, MA, chair on “Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Update.” This guideline updates recommendations on use of alpelisib, and the role of biomarkers and CDK4/6 inhibitors. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey. TRANSCRIPT [MUSIC PLAYING] SPEAKER: 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] BRITTANY HARVEY: 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 podcasts.asco.org. My name is Brittany Harvey. And today I'm interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute in Boston, Massachusetts, chair and lead author on endocrine treatment and targeted therapy for hormone receptor-positive HER2 negative metastatic breast cancer ASCO guideline update. Thank you for being here, Dr. Burstein. HAROLD BURSTEIN: Glad to be with you. BRITTANY HARVEY: First I'd like to note that ASCO takes great care in the development of its guidelines in 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. Burstein, do you have any relevant disclosures that are related to this guideline topic? HAROLD BURSTEIN: I do not. BRITTANY HARVEY: Great, thank you. Then let's delve into the content of this guideline. So first, what prompted the update of this guideline and what is the focus of this update? HAROLD BURSTEIN: So this guideline focuses on metastatic breast cancer, and in particular, estrogen receptor-positive HER2 negative metastatic breast cancer. Worldwide in 2021, actually breast cancer became the most commonly diagnosed cancer in the world, excepting superficial skin cancers. And so it is a true global health problem. And the most common type of breast cancer is estrogen receptor-positive HER2 negative breast cancer, which accounts for 70% to 75% of all cancer diagnoses in the breast cancer space, and as a consequence, also accounts for 70% to 75% of the cases of metastatic breast cancer. So it's really important from a public health point of view and a quality point of view, both in the United States and globally, to have current up-to-date guidance for the management of this most common form of breast cancer that we have. In addition, there have been several innovations in the way of targeted therapies that are coming into place for advanced ER-positive breast cancer. And increasingly, we are using genomic tests to help us understand how best to treat patients with advanced ER-positive breast cancer. So those two initiatives-- the interest in genomic testing and the use of targeted therapies-- all warranted and justified an update to the guidelines. BRITTANY HARVEY: Great. Thank you for reviewing that landscape of where we are in clinical practice for this guideline. So then I'd like to review the key recommendations that this guideline addresses. So first, should alpelisib be given to post-menopausal women and to male patients with hormone receptor-positive HER2 negative PIK3CA-mutated advanced or metastatic breast cancer? HAROLD BURSTEIN: So alpelisib, as you indicated, is a new drug. It is now FDA approved. And it is a protein kinase targeted inhibitor. And it goes after the PIK3CA-mutated tumors. And in a seminal study called the SOLAR-1 study, there was randomization to endocrine therapy alone with fulvestrant or endocrine therapy plus alpelisib for ER-positive HER2 negative breast cancer. And that study showed two important things. First was that in women whose tumors did not have a PIK3CA mutation, there was no benefit for alpelisib. However, in the women whose tumors did have a PIK3CA mutation, there was an improvement in progression-free survival with the use of this targeted drug alpelisib. So based on that, the guidelines now incorporate alpelisib into the treatment algorithm. And as a corollary, it means that all patients who have ER-positive metastatic breast cancer now need testing of the tumor to see if they have a PIK3CA mutation because that's going to guide therapy. In the guideline, we now suggest that this be a standard thing to do-- to test all tumors for PIK3CA mutation. And in those cases where there is a PIK3CA mutation to add alpelisib-based therapy with endocrine treatment typically in second or subsequent lines of therapy. BRITTANY HARVEY: Great. And thank you for reviewing the evidence base behind that recommendation. So next, what is recommended regarding the role of biomarkers in treatment selection for patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So there are two different ways of thinking about biomarkers. One is traditional biomarkers, such as estrogen receptor, progesterone receptor, and HER2. Those are familiar to all clinicians who have been dealing with breast cancer. The second is to think about some of the newer technologies, including tumor genomic sequencing and the kind of mutational analysis we just discussed with the PIK3CA mutations. So in the breast cancer space, there are some important innovations in that latter genomic or genetic testing. One, of course, is the PIK3CA mutation testing that we now recommend for all cancers. That can be done on the primary tumor, or it can be done on cell-free or circulating tumor DNA samples from the bloodstream in most cases. The other kind of testing we do relates to ESR1 mutations. And one of the reasons that tumors become resistant to aromatase inhibitors is that they acquire mutations in the estrogen receptor itself, so-called ESR1 activating mutations. Those mutations mean that the estrogen receptor is on even in the absence of estrogen. And that accounts for probably 50% to 60% of the resistance that we see in treatment with aromatase inhibitors. So the panel really struggled with this because, on the one hand, this is not a uniformly accepted way to decide how to treat patients. On the other hand, there are a lot of data that women whose tumors have ESR1 mutations get negligible benefit from ongoing use of aromatase inhibitor therapy. So this recommendation fell into sort of our practice suggestions, which is that if you have the information on ESR1, then it probably is the case that there's very little, if any, role for ongoing aromatase inhibitor treatment. This fell short of the highest level in endorsement because, first, it's not a uniformly tested assay. And secondly, it's important to remember that these tumors can still benefit from ongoing anti-estrogen therapy with different anti-estrogens like fulvestrant. And finally, and perhaps this is the most practical issue, the way you become ESR1 mutated is usually through exposure to aromatase inhibitors. And if you've already had a patient with extensive exposure to AIs, and they need ongoing anti-estrogen therapy in the metastatic setting, it usually means you're switching treatment anyway. So that's an example of where we're sort of on the frontier of thinking about dynamic changes in the tumor as a way to select treatment for ER-positive metastatic disease. BRITTANY HARVEY: Great. That's helpful for a clinical interpretation of the recommendations and incorporating these into practice. So the final question that was addressed in this focused update was, what is the role of CDK4/6 inhibitors in the treatment of patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So CDK4/6 inhibitors are another tyrosine kinase inhibitor class of drugs that has really emerged as an important part of first-line therapy for ER-positive metastatic disease. There have been multiple randomized trials looking at either first-line therapy with an aromatase inhibitor with or without a CDKI4/6 inhibitor, or second-line treatment typically with fulvestrant with or without a CDKI4/6 inhibitor in the metastatic setting. And the panel was able to update the guidance here based on the maturation of multiple randomized trials, as well as extensive subset analyses that have been performed by investigators associated with the individual pharmaceutical-led studies and by the FDA itself. So here are some important takeaways. The first is that in long-term follow-up, these drugs as a class are improving overall survival for women with ER-positive HER2 negative metastatic breast cancer. And for that reason, they are a very important part of the standard armamentarium for ER-positive disease. It's important to say that they also delay the onset of need for chemotherapy, and in general, are associated with a very well preserved quality of life. So this is a big win for patients with ER-positive metastatic breast cancer. We typically recommend them in the first-line setting. So if a patient has de novo metastatic disease, then they should get an endocrine therapy such as an aromatase inhibitor with a CDK4/6 inhibitor. If they've previously had adjuvant aromatase inhibitor treatment or recur while on adjuvant endocrine therapy, we often move to fulvestrant plus a CDKI4/6 inhibitor. Both settings have shown substantial benefit for this class of drugs. It's important that clinicians understand the side effects of these drugs. Neutropenia and diarrhea are common side effects associated with the various drugs. And because of the prevalence of ER-positive metastatic disease, it's really important for clinicians and all those who care for advanced breast cancer patients to know how to manage those side effects carefully. The panel discussed controversial issues, I suppose you might say, in the management. What about patients who have truly minimal metastatic disease? There aren't a lot of data on how best to think about those patients. And we all can imagine on a case-by-case basis an individual who might not need a CDK4/6 inhibitor at a given moment in time. But what was impressive when we pulled all the data was that in subset analyses, it's really hard to find a group of patients that does not benefit from the incorporation of these drugs. So that included premenopausal women who also get concurrent ovarian suppression and then endocrine therapy plus the CDK4/6 inhibitor. It included women with bone-only metastatic disease. It included women whose tumors were ER-positive but PR negative, or had other variations in ER expression. It included patients who had less rather than more metastatic cancer, including visceral disease. So in the literature, one is hard-pressed to see a subset that does not benefit meaningfully from this class of drugs. So we really wanted to reiterate in the algorithms just how important these are. They should be the standard first-line treatment for metastatic disease either paired with an AI or with fulvestrant. And so one of the other nice things that the update gave us was the opportunity to put in some fresh sort of algorithm flow sheets. I would very much encourage people to look at that. They make fantastic PowerPoint or downloadable Twitter documents if you are so inclined. But it's very clear the way the treatment should flow, which is the initial therapy is endocrine treatment plus a CDK4/6 inhibitor. While the patients are getting that, we typically test for PIK3CA mutations. In second line, if it's a PIK3CA mutated, you have the option of using alpelisib. You also might consider an older drug for PIK3CA wild type tumors called everolimus. We reiterated that recommendation in the guideline. Finally, one more thing to touch on that is emerging in the guidelines we generated and in the parallel guideline process for the ASCO guidance on chemotherapy-resistant or refractory breast cancer is the importance of genetic testing all patients who have metastatic breast cancer to look for the possibility of a BRCA1 or BRCA2 deleterious mutation, because there now is FDA approval for PARP inhibitors in the setting of metastatic disease. And one of the interesting things is that as we test more and more, we're seeing that not all the patients who are found to have a BRCA1 or 2 mutation meet the classic criteria for genetic testing-- strong family history, or say, triple-negative breast cancer. So it's really important to test, because that class of drugs, the PARP inhibitors, can be immensely helpful in women with ER-positive metastatic disease when they harbor a BRCA1 or 2 mutation. One of the things the guideline panel wrestled with and ended up putting into the sort of clinical discussion, as opposed to the strong guidance, was the 1% of patients who have PALB2 mutations. So PALB2 mutation, another hereditary predisposing factor for breast cancer. Most tumors that arise in PALB2 mutation carriers are in fact estrogen receptor positive. And a very small study, now published in the JCO, has suggested that those patients have a very high likelihood of response to PARP inhibitors. Because there were only like 15 patients in that cohort, we didn't feel that this warranted clear endorsement in the guidelines. But at the same time, everyone on the panel acknowledges that this is an active drug in that rare subset of tumors with PALB2 mutations in addition to the BRCA1 or 2 mutations. So the takeaway here is that genetic testing should be standard for all patients with advanced metastatic breast cancer to see if the patient is a candidate for a PARP inhibitor-based therapy. BRITTANY HARVEY: Definitely. Well, thank you for reviewing all of those updated recommendations and highlighting some of the ones that were still relevant to this guideline. HAROLD BURSTEIN: Work in progress. BRITTANY HARVEY: Yeah, definitely. And then finally, what is the importance of this guideline update? And how will it impact both clinical practice and what does it mean for patients? HAROLD BURSTEIN: Well, I think guidelines like this have multiple purposes. The first is to sort of describe the state of the art. And while breast cancer is a very common disease, and most clinicians who take care of a lot of cancer patients will see a lot of advanced breast cancer, I think it's still helpful to articulate the rationale for these treatment recommendations. And one of the great things about the ASCO guideline process is the thoroughness of the literature review, the thoroughness of the search to make sure we're including all important publications, and the thoughtfulness that the panel, which includes experts, patient advocates, quality of life expertise, all those things bring to bear on really thinking through what makes sense and what does not for our patients based on the best science available. So I think it is an important activity to really sort of benchmark where we're at. The second thing we've tried to do in the guideline is to introduce areas of nuanced discussion, because not every patient is the same. And I think for those who are interested and take the time to read the guideline, there really is a very nice discussion about how our panel thought about when best to use this approach and when to use a different approach. Third, there's extensive discussion of the side effects and the appropriate management of the side effects. These are drugs that do carry risks. And while by oncology standards, many of them are, quote, "well tolerated," unquote, there's no doubt that there are side effects to these drugs. And it's important for clinical teams to know how to manage them. Finally, I think by putting forward all the evidence, you make clear to investigators, to drug companies, to patients and advocates, and others who are involved in the review of new drugs what the benchmarks are and what the criteria should be for designing clinical trials and for approving new drugs. And I think we've done a nice job of framing that discussion quite handsomely in this guideline and to all of the ASCO guidelines. BRITTANY HARVEY: Great. Well, thank you so much for your work on this guideline update and for taking the time to speak with me today, Dr. Burstein. HAROLD BURSTEIN: Happy to join you and thanks very much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast cancer guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at SurveyMonkey.com /r/ascoguidelinesurvey. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]