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2 episodes with pik3ca
3 episodes with pik3ca
3 episodes with pik3ca
2 episodes with pik3ca
Love the episode? Send us a text!In this special episode of Breast Cancer Conversations, host Laura Carfang speaks with Dr. Troso about the evolving role of DNA testing in breast cancer care. Together, they break down the three main types of testing:Hereditary genetic testing: Identifying inherited mutations such as BRCA1, BRCA2, and PALB2 (among others) that increase cancer risk and influence prevention and treatment decisions.Somatic (tumor) testing: Analyzing mutations within the tumor itself—such as PIK3CA or ESR1 mutations—to guide targeted therapies and manage resistance in advanced disease.Circulating tumor DNA (ctDNA) testing: Also known as a liquid biopsy, this emerging tool uses blood tests to detect cancer DNA fragments. It holds promise for monitoring recurrence, guiding treatment earlier, and advancing clinical trials.Tune into this Special!
“She's triple negative and has a very, very aggressive tumor. Instead of going on spring break that year, she sat in our chemo room and got chemo. Her friends from college are good to try to keep her involved and try to surround her and encourage her, but they're right now in very, very different spots in their lives. She's fighting for her life; her friends are fighting for the grade they get in a class—and that's different,” ONS member Kristi Orbaugh, MSN, NP, AOCN®, AOCNP®, nurse practitioner at Community Hospital North Cancer Center in Indianapolis, IN, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about metastatic breast cancer in adolescent and young adult patients. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 This podcast is sponsored by Lilly and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 354: Breast Cancer Survivorship Considerations for Nurses Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 345: Breast Cancer Screening, Detection, and Disparities Episode 307: AYAs With Cancer: Financial Toxicity Episode 300: AYAs With Cancer: End-of-Life Care Planning ONS Voice articles: ‘Cancer Ghosting' May Add Another Layer of Emotional Burden for Patients Discoveries in Race-Related Breast Cancer Biomarkers May Improve Precision Treatments What Is HER-2-Low Breast Cancer? What Oncology Nurses Need to Know About Supporting AYAs With Cancer ONS books: Guide to Breast Cancer for Oncology Nurses Oncology Nursing Forum articles: An Integrative Review of the Role of Nurses in Fertility Preservation for Adolescents and Young Adults With Cancer Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes Relations of Mindfulness and Illness Acceptance With Psychosocial Functioning in Patients With Metastatic Breast Cancer and Caregivers ONS huddle cards: Altered Body Image Fertility Preservation Sexuality Other ONS resources: Breast Cancer Learning Library Fertility Preservation in Individuals With Cancer ONS Biomarker Database American Cancer Society's breast cancer resources American Society of Clinical Oncology continuing education resources Elephants and Tea Life, Interrupted Livestrong National Cancer Institute's breast cancer resources Stupid Cancer Young Survival Coalition To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “When we use ‘adolescent and young adult,' we're really talking about age 19–35. Some groups will say 15–39, but right around that age. When we think about that age, think about what all could be going on during those ages. Late teenagers, they may be going off to college, they may be graduating high school, trying to set up their own life, trying to become independent from mom and dad. If you're talking about early to mid 30s, you could be talking about young parents, young career folks. So, just setting that into place makes you realize this can be a very tumultuous time for folks.” TS 2:06 “Unfortunately, this group tends to have more aggressive subtypes. We see more triple-negative in this group. We see more hormone-negative, HER2-positive in this group. Normal breast cancer cells should be stimulated by hormone. They are stimulated by hormones. So when you have a breast cancer cell that is not driven by hormones, it's much more difficult to treat. We tend to see more aggressiveness in these tumors. We also see a higher incidence in non-Caucasian folks in this age group compared to the older age groups.” TS 4:53 “I think we have gotten much better about understanding the importance of fertility preservation and getting reproductive endocrinologists in, sooner rather than later. If we have earlier-stage cancers and we have patients that want to try to preserve eggs, preserve fertility, sperm banking. … If you have that time to talk to them—maybe a 21-year-old—the primary thing on her mind is not how many children she wants to have one day. Maybe she's not even thought about having kids yet. It's still a question you need to [ask]. Do you want to try to preserve fertility? Do you want to try to harvest some eggs? That's a conversation that needs to be had and is very, very important for that age group.” TS 10:35 “One thing that helps is if you can get them [into] reputable support groups with people their own age that are going through what they're going through. Someone else that doesn't have hair, someone else that isn't going to make it to the big board meeting or isn't going to get the promotion this year because they've had to take a medical leave. Someone else that understands it differently.” TS 16:47 “In breast cancer, many of those biomarkers just get reflexed. And what I mean by reflexed is a breast cancer pathology comes through, or a breast cancer specimen comes through, and it just automatically gets tested for X, Y, Z. HER2 and of course ER/PR. Now we understand that we don't just need to know whether they're HER2 positive or HER2 negative. We need to know: What is the IHC score? And even if the IHC score is zero, is there any membrane staining? And then we need to know what's their ESR1, their PTEN, their AKT, their PIK3CA. Those are so important to know.” TS 18:11 “I think it's important to try to remember what our priorities were when we were in our 20s—what our priorities were when we were starting out as young mothers or starting out our career. Because that's where these folks are. … I can't imagine in the midst of college, when I'm trying to be independent, to suddenly have to be at home and rely on my mom to take me to my chemo appointment. … So I think one really important bias is to remember where they are in the developmental stages of life. They're not 40-something. They haven't lived X amount of life, and we need to take a step back and try to remember when we were their age, what was important to us? Where were our priorities at that point? And then hear them when they're telling us what's important to them.” TS 29:22 “From a female standpoint … we frequently throw these patients into menopause or have early menopausal symptoms, and I think we forget how devastating that can be. … They now are at higher risk for osteopenia or osteoporosis. … And then we tell people, ‘Be as normal as possible, get back and do those normal things.' Well, they're in a relationship, and they want to be intimate [but] suddenly having sexual intercourse is incredibly painful. Or if it's not painful, sometimes they've just lost pure interest in that. They don't feel confident about their body. All of those things need to be addressed because patients are trying to live each day as normally as possible.” TS 31:55
BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.” In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients. Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers. One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response. In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use. Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer. “One limitation to be considered is the low PPA for ERBB2 CNA detection.” By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology. DOI - https://doi.org/10.18632/oncotarget.28761 Correspondence to - David Spetzler - dspetzler@carisls.com Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Neil M. Iyengar, MD Due to their wild-type inhibition, first-generation PIK3CA inhibitors for HR+/HER2- advanced breast cancer were limited by significant toxicities, including hyperglycemia, rash, and diarrhea. But now, mutation-specific PIK3CA inhibitors could help improve tolerability and adherence as well as simplify dosing strategies—all while maintaining efficacy. To learn more about the efficacy and safety of current and emerging PIK3CA-targeted therapies, Dr. Charles Turck speaks with Dr. Neil Iyengar, Co-Director of the Breast Oncology Program and Director of Cancer Survivorship Service at Winship Cancer Institute at Emory University.
Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Neil M. Iyengar, MD Due to their wild-type inhibition, first-generation PIK3CA inhibitors for HR+/HER2- advanced breast cancer were limited by significant toxicities, including hyperglycemia, rash, and diarrhea. But now, mutation-specific PIK3CA inhibitors could help improve tolerability and adherence as well as simplify dosing strategies—all while maintaining efficacy. To learn more about the efficacy and safety of current and emerging PIK3CA-targeted therapies, Dr. Charles Turck speaks with Dr. Neil Iyengar, Co-Director of the Breast Oncology Program and Director of Cancer Survivorship Service at Winship Cancer Institute at Emory University.
In this episode, Kevin Kalinsky, MD, MS, FASCO, and Sara M. Tolaney, MD, MPH, discuss the most clinically relevant data in breast cancer presented at the 2025 ASCO Annual Meeting, including: DESTINY-Breast09: phase III trial of trastuzumab deruxtecan with or without pertuzumab vs THP as first-line treatment of HER2-positive advanced/metastatic breast cancerASCENT-04/KEYNOTE-D19: phase III trial of first-line sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab in PD-L1–positive advanced TNBCSERENA-6: phase III trial of ctDNA-guided switch to camizestrant plus CDK4/6i vs continued AI plus CDK4/6i following ESR1 mutation emergence in HR-positive/HER2-negative advanced breast cancerINAVO120: OS from phase III study of first-line inavolisib/PBO plus palbociclib plus fulvestrant in PIK3CA-mutated, HR-positive/HER2-negative, endocrine-resistant advanced breast cancerPresenters:Kevin Kalinsky, MD, MS, FASCOProfessor of MedicineLouisa and Rand Glenn Family Chair in Breast Cancer ResearchWinship Cancer InstituteEmory UniversityAtlanta, GeorgiaSara M. Tolaney, MD, MPHChief, Breast OncologyDana-Farber Cancer InstituteAssociate Professor of MedicineHarvard Medical SchoolBoston, MassachusettsContent based on an online CME program supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc, Gilead Sciences, Inc., Lilly, Novartis Pharmaceuticals Corporation, and Stemline Therapeutics, Inc.Link to full program: https://bit.ly/4lFS4BC
Welcome to the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Erika Hamilton from the Sarah Cannon Research Institute to discuss the latest breakthroughs in breast cancer presented at the ASCO 2025 annual meeting. We dived into five key abstracts that could change the landscape of breast cancer treatment: 1. INAVO120: observed overall survival data with the combination of inavolisib, with palbociclib and fulvestrant for patients with PIK3CA mutated hormone receptor-positive, HER2-negative advanced breast cancer. 2. SERENA-6: camizestrant use in patients with emerging ESR1 mutations using ctDNA, showed significant improvement in progression-free survival. 3. VERITAC-2: vepdegestrant showed superior progression-free survival compared to fulvestrant, particularly in ESR1 mutated patients. 4. DESTINY-Breast09: significant improvement in progression-free survival with TDXd plus pertuzumab in frontline HER2-positive metastatic breast cancer, challenging the traditional CLEOPATRA regimen THP. 5. ASCENT-04: promising results of sacituzumab combined with pembrolizumab in PD-L1 positive triple-negative breast cancer. Join us for an insightful discussion on these practice changing/informing studies and their implications for clinical practice. YouTube: https://youtu.be/5XvrOn2p0jc Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more updates on treatment algorithms, recent approvals, and conference highlights!
In this episode, we unpack game-changing insights from ASCO 2025 with a spotlight on breast cancer. Joining us is Dr. Adam Brufsky, a trailblazing oncologist and professor at the University of Pittsburgh, with 30 years of experience, whose expertise has helped shape the direction of treatment. Trials discussed include the SERENA-6 trial, which examines camizestrant plus CDK4/6 inhibitors in HR-positive, ESR1 mutation breast cancer; the DESTINY-Breast09 trial, highlighting trastuzumab deruxtecan in combination with pertuzumab; and the INAVO120 trial, revealing inavolisib's triplet therapy response in PIK3CA-mutated, HR-positive, HER2-negative disease. Join us for a deep dive into these game-changing findings and their impact on patient care.Studies discussed in the episode:SERENA-6DESTINY BREAST 09INAVO 120For 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.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.
Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications
The approach to ESR1 and PIK3CA mutations in patients with hormone receptor–positive metastatic breast cancer continues to evolve. What role does circulating tumor DNA (ctDNA) play in treatment decisions? How should oncologists best approach patients with PIK3CA mutations who subsequently develop ESR1 mutations? VK Gadi, MD, PhD, professor and director of medical oncology and deputy director of the University of Illinois Cancer Center in Chicago, discusses with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology, how recent data are informing care for patients with comutations. “We now have at least one ESR1-targeting drug out there, and more to come,” Dr. Gadi explains. “Elacestrant is the drug I'm of course referencing, and that is used essentially like a single agent and works well for those patients. Even when they have, for example, PIK3CA mutations present.” He and Dr. Figlin consider when to act on ctDNA findings and potential future strategies. Dr. Gadi reported no relevant financial relationships. Dr. Figlin reported various financial relationships.
Featuring an interview with Dr Sara A Hurvitz, including the following topics: Role of endocrine therapy in the management of HER2-positive breast cancer; implications of the Phase III PATINA study (0:00) Case: A woman in her mid 60s with node-negative, HR-positive, HER2-negative localized breast cancer and a Recurrence Score® of 28 (8:38) Available data guiding the selection of an adjuvant CDK4/6 inhibitor (12:49) Selection of a CDK4/6 inhibitor in the metastatic setting (23:16) Available therapies for patients with HR-positive metastatic breast cancer (mBC) and PIK3CA mutations; implications of the Phase III INAVO120 study (29:17) Case: A woman in her early 60s with HR-positive, HER2-negative mBC with short duration of benefit from a first-line CDK4/6 inhibitor and an aromatase inhibitor (AI) and coexisting PIK3CA and ESR1 mutations (37:11) Available data with approved and investigational oral SERDs (selective estrogen receptor degraders) (43:23) Case: A woman in her early 70s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after durable responses to first-line endocrine therapy and second-line CDK4/6 inhibitor with an AI (51:38) Selection of therapy for patients with HR-positive mBC and coexisting targetable genetic mutations (53:11) Case: A woman in her late 50s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after first-line CDK4/6 inhibitor with an AI (1:00:17) CME information and select publications
Send us a textWelcome to The Oncology Journal Club Podcast Series 3! Proudly produced by The Oncology NetworkThree respected oncologists dive deep into the most significant research presented at ASCO GI 2025, bringing you practice-changing insights amidst a backdrop of political uncertainty affecting medical research.Professor Chris Karapetis joins hosts Professor Craig Underhill and Professor Christopher Jackson to unpack ground-breaking colorectal cancer studies that are reshaping treatment paradigms. The conversation explores how targeted therapies are dramatically improving survival rates, with the DEEPER study demonstrating cetuximab's superiority over bevacizumab for left-sided RAS wild-type disease, achieving an impressive 50-month median survival when combined with chemotherapy.The experts dissect the BREAKWATER trial, which shows promising benefits of combining encorafenib and cetuximab with chemotherapy for notoriously aggressive BRAF-mutant colorectal cancer. This combination achieved a 61% response rate versus 40% with standard care, with responses lasting significantly longer – representing a potential new standard of care for this difficult-to-treat subgroup.Perhaps most surprisingly, our panel discusses how an inexpensive, familiar medication – aspirin – could reduce colorectal cancer recurrence by 40% in patients with PIK3CA mutations according to the ALASCCA study. This finding highlights how molecular profiling is becoming essential across treatment stages, not just for expensive targeted therapies but also for optimising use of accessible interventions.The discussion extends to exciting developments in pancreatic cancer with a novel pan-RAS inhibitor showing meaningful activity, and advancements in immunotherapy for MSI-high colorectal cancer, confirming combination therapy's superiority. For gastrointestinal oncologists navigating an increasingly complex treatment landscape, this episode offers crucial insights to optimise patient outcomes through precise, personalised approaches.Subscribe to The Oncology Newsletter for regular updates on the latest cancer research and join our community at oncologynetwork.com.au.The Oncology Podcast - An Australian Oncology Perspective
Dr Kaklamani discusses the mechanism of action of inavolisib, the importance of the addition of this agent to the HR-positive metastatic breast cancer treatment paradigm, and considerations for early biomarker testing in patients with breast cancer.
Breast cancer treatment today is becoming more personalized and more precise. Precision medicine is rapidly expanding the options patients have for treating their cancer while helping them maintain a desired quality of life. A common mutation in breast cancer called PIK3CA affects more than 1 in 3 people with breast cancer, making it harder to treat. This mutation often leads to worse outcomes for these patients compared to others. Scientists are now developing new treatments that target this mutation specifically, aiming to reduce side effects and improve treatment outcomes, such as shrinking tumors or preventing disease progression. Today, we are speaking with Dr. Sarah Sammons of Dana-Farber Cancer Institute to explore the exciting new possibilities brought by personalized medicine, including whether it can help slow disease progression and how it can it improve patients' abilities to potentially live more active and productive lives while on treatment.
In today's episode, supported by Genentech, we had the pleasure of speaking with Komal Jhaveri, MD, FACP, about the clinical use of inavolisib (Itovebi) for patients with hormone receptor (HR)–positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. Dr Jhaveri is section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Jhaveri discussed the importance of having a PI3K inhibitor available for the treatment of patients with HR-positive metastatic breast cancer, advice for managing inavolisib-related adverse effects, and best practices for early biomarker testing in patients with breast cancer.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms." Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients. “Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.” Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment. The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment. “Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.” Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified. With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized. In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care. DOI - https://doi.org/10.18632/oncotarget.28680 Correspondence to - Andrew A. Davis - aadavis@wustl.edu About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
In this JCO Article Insights episode, Giselle de Souza Carvalho provides a summary on "Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies" by Bhardwarj, et al and "US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations" by Dilawari et al published in the Journal of Clinical Oncology. TRANSCRIPT Giselle Carvalho: Hello and welcome to JCO Article Insights episode for the December issue of the Journal of Clinical Oncology. I'm your host Giselle Carvalho, Medical Oncologist in Brazil focusing on breast cancer and melanoma skin cancers and one of the ASCO Editorial Fellows at JCO this year. Today, I will be discussing two articles. The first one is “Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies,” and the second one is the “US FDA Approval Summary on Capivasertib with Fulvestrant for HR-positive HER2-negative Locally Advanced or Metastatic Breast Cancer with PIK3CA/AKT1/PTEN Alteration.” As we know, 65% to 70% of all breast cancers are HR-positive HER2-negative and this is also the most common subtype of metastatic breast cancer. The current standard of care for frontline therapy of patients with luminal metastatic disease is a CDK4/6 inhibitor in combination with endocrine therapy. However, as new endocrine and targeted therapies gain approval, choosing the best systemic therapy upon disease progression after frontline therapy is a topic of ongoing debate. Nearly 40 to 50% of HR-positive breast cancers have actionable genomic alterations and molecular testing should be a routine recommendation for patients with metastatic HR-positive HER2-negative disease. This can be performed repeating tissue biopsy at the time of progression or from archival tissue. Treatment options after progression on CDK4/6 inhibitors include alpelisib in combination with fulvestrant in patients with PIK3CA mutant tumors as seen in the SOLAR-1 trial, or capivasertib with fulvestrant in patients with a tumor mutation in (PI3K)–AKT–PTEN pathway as seen in the CAPItello-291 study, which will be discussed further. In approximately 30% of patients, progression on frontline endocrine plus CDK4/6 inhibitor treatment is caused by endocrine resistance, frequently involving activating mutations in ESR1. For those tumors, elacestrant, an oral SERD is an option as demonstrated in the EMERALD trial. For patients with a BRCA mutation, PARP inhibitors represent another option. If no mutations are detected, everolimus, an mTOR inhibitor, can be used based on the BOLERO-2 results. The phase 2 MAINTAIN and PACE trials, along with the phase 3 postMONARCH trial support changing the endocrine therapy backbone with or without switching the CDK4/6 inhibitor. In less resourced areas, fulvestrant monotherapy is still an option to delay cytotoxic chemotherapy, though its efficacy is limited when used as a single agent. Finally, after progression on at least one line of chemotherapy, antibody drug conjugates including sacituzumab govitecan or trastuzumab deruxtecan may be an option. Now focusing on the PI3K AKT PTEN signaling pathway, activating mutations in PIK3CA and AKT1 and inactivating alterations in PTEN occur in approximately half of luminal breast cancers. In June 2023, the CAPItello-291 trial was published and treatment with fulvestrant plus capivasertib, a PTEN AKT inhibitor, demonstrated a 3.6 month PFS benefit compared to fulvestrant alone, regardless of the presence of AKT pathway alterations. However, for those with tumors without AKT pathway alteration, an exploratory analysis showed that although there was a numerical improvement in PFS, it did not meet statistical significance, indicating that the biomarker positive population primarily drove the positive results noted in the overall population. Therefore, capivasertib plus fulvestrant was approved by the US FDA in November 2023 exclusively for patients with PI3K/AKT1/PTEN tumor alterations after progression on an aromatized inhibitor with or without a CDK4/6 inhibitor. The approved schedule of capivasertib is slightly different from that of other agents used in breast cancer. It is 400 milligrams taken orally twice a day for four days per week every week in a 28-day cycle in combination with fulvestrant. Diarrhea, rash and hyperglycemia were the most commonly reported grade three or four adverse events in the interventional group. I would like to highlight that even though the CAPItello trial excluded patients with glycosylated hemoglobin levels higher than 8% or those diagnosed with diabetes who required insulin, hyperglycemia occurred in 19% of biomarker positive patients treated with capivasertib, with nearly 2% of this population experiencing grade 3 or 4 hyperglycemia and some patients experiencing life threatening outcomes such as diabetic ketoacidosis. By way of comparison, hyperglycemia of any grade was three times higher with alpelisib therapy in the SOLAR-1 trial, occurring in 64% of the patients and grade three or higher hyperglycemia was seen in 37% of the patients. Diarrhea was the most common treatment related adverse event experienced by 77% of the biomarker positive population. Prompt use of the antidiarrheal drugs when needed, such as loperamide must be encouraged as untreated diarrhea can lead to dehydration and renal injury. Cutaneous rash occurred in 56% of the biomarker positive population in the interventional group and 15% experienced a grade 3 or 4 rash. Nearly half of the patients with cutaneous adverse reactions required treatment and this was the leading reason for dose reduction of capivasertib. In the biomarker positive population, the improvement in medium PFS were 4.3 months by investigator assessment. Overall survival data from the CAPItello-291 trial is still immature, but quality of life data was recently published in September this year and was assessed by the 30 item QLQ C30 questionnaire and the QLQ BR23, the breast module. According to Oliveira et al, global health status and quality of life were maintained for a longer period with capivasertib fulvestrant than with placebo fulvestrant except for symptoms of diarrhea which were significantly worse in the capivasertib group. The median time of deterioration of global health status and quality of life was twice as long in the capivasertib group being almost 25 months versus 12 months in the placebo fulvestrant group. These data reinforced the use of capivasertib in combination with fulvestrant for the treatment of HR-positive HER2-negative advanced breast cancer patients with PIK3CA/AKT1/PTEN tumor alterations who have progressed after an aromatase inhibitor-based therapy with or without a CDK4/6 inhibitor. Thank you for listening to JCO Article Insights. This is Giselle Carvalho. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. See you next time. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
Recent advances in hormone receptor–positive, HER2-negative metastatic breast cancer have led to questions about the timing of genetic testing and the optimal treatment choices for patients. “I, like many others, have changed my personal practice,” says Azka Ali, MD, a medical oncologist at the Cleveland Clinic Taussig Cancer Institute in Ohio. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss what newly approved medications for patients with PIK3CA mutations mean for oncologists. “I think the breast cancer landscape is changing faster than we can all keep up with it,” Dr. Ali explains. She breaks down current genetic testing concerns and how she approaches treatment decisions that sometimes take place in a “data-free zone.” Dr. Ali reported no relevant financial disclosures. Dr. Figlin reported various financial relationships.
Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain dive deep into the recent FDA approval of Inavolisib for metastatic hormone receptor-positive breast cancer, based on the groundbreaking INAVO120 study. Join us as we chat with Dr. Komal Jhaveri, a medical oncologist and senior author of the study from Memorial Sloan Kettering Cancer Center. We explored the study design, key findings, and the implications of this new treatment option for patients with PIK3CA mutations. Key topics discussed include: • Overview of the INAVO120 study and its significance • The unique patient population targeted in the study • Key findings, including the impressive improvement in progression-free survival (PFS) • Side effects and management strategies for patients • The importance of genetic testing in treatment decisions Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode provides valuable insights into the evolving landscape of breast cancer treatment. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! #OncologyBrothers #BreastCancer #ENAVOLacib #PIK3CA #CancerResearch #MedicalPodcast #Oncology Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com
A new PIK3Ca inhibitor is approved for breast cancer.
Join us for an informative discussion about PIK3CA testing and treatment with Dr. Neil Iyengar
Dr Jhaveri discusses the INAVO120 trial of inavolisib plus palbociclib and fulvestrant in PIK3CA-mutant, HR-positive metastatic breast cancer.
El Dr. Juan Carlos Samamé Pérez-Vargas, oncólogo médico, vicepresidente de LABCA, adscrito a la Clínica San Felipe y Hospital Loayza en Lima, Perú, en conjunto con el Dr. William Mantilla, hemato-oncólogo, jefe de la Unidad Funcional de Cáncer de Mama en la Fundación CTIC en Bogotá, Colombia, nos comentan sobre lo más destacado en cáncer de mama presentado en el Congreso de ASCO 2024, resaltando los siguientes estudios: Enfermedad temprana NATALEE: estudio fase III, multicéntrico, aleatorizado, abierto, que evaluó la eficacia y seguridad de ribociclib con terapia endocrina como tratamiento adyuvante en pacientes con cáncer de mama temprano RH+/HER2- y ganglios negativos. Análisis de NCBD: evaluación de la eficacia de la terapia endocrina neoadyuvante en cáncer de mama HER2 bajo frente a HER2-. La respuesta de los pacientes a la terapia incluyó respuesta patológica completa, respuesta patológica parcial, respuesta patológica estable o progresión en el tumor primario al momento de la resección. FLEX: asociación del índice MammaPrint y el resultado a 3 años de pacientes con cáncer de mama en etapa temprana RH+/HER2- tratados con quimioterapia con o sin antraciclinas. RxPONDER: estudio que evaluó la correlación de los niveles de hormona antimülleriana en la identificación de pacientes premenopáusicas con cáncer de mama RH+/HER2- con ganglios positivos, con probabilidad de beneficio de la quimioterapia adyuvante. Enfermedad avanzada postMONARCH: estudio fase III, aleatorizado, doble ciego, controlado con placebo que comparó la eficacia de abemaciclib más fulvestrant vs. placebo más fulvestrant en pacientes con cáncer de mama avanzado/metastásico RH+/HER2-, tras la progresión a un tratamiento previo con un inhibidor de CDK 4/6 y terapia endocrina. INAVO120: estudio fase III, aleatorizado, doble ciego, controlado con placebo que evaluó la eficacia y seguridad de inavolisib más palbociclib más fulvestrant vs. placebo más palbociclib más fulvestrant en pacientes con cáncer de mama localmente avanzado o metastásico, con mutación de PIK3CA, RH+/HER2-. SACI-IO HR+: estudio fase II, aleatorizado, que evaluó el uso de sacituzumab govitecán con o sin pembrolizumab en pacientes con cáncer de mama metastásico RH+/HER2-. DESTINY-Breast06: estudio fase III, aleatorizado, multicéntrico, abierto de trastuzumab deruxtecán vs. quimioterapia a elección del investigador en pacientes con cáncer de mama HER2-bajo RH+, cuya enfermedad ha progresado durante la terapia endocrina en el entorno metastásico. EMERALD: estudio fase III, abierto, multicéntrico, aleatorizado, que comparó la terapia combinada de mesilato de eribulina más pertuzumab más trastuzumab con paclitaxel o docetaxel más pertuzumab más trastuzumab, como tratamiento de primera línea en pacientes con cáncer de mama HER2+ localmente avanzado/metastásico. OptiTROP-Breast01: estudio fase III, aleatorizado, donde se comparó el uso de sacituzumab tirumotecán con la elección de quimioterapia del médico en pacientes con cáncer de mama triple negativo localmente recurrente o metastásico que habían recibido dos o más terapias previas, incluyendo al menos una para el contexto metastásico. Fecha de grabación: 10 de junio de 2024. Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.
Dr. Allison Zibelli and Dr. Megan Kruse discuss the potential benefit of endocrine therapy in ER-low breast cancer; the efficacy and tolerability of triplet therapy in PIK3CA-mutated, HER2-negative locally advanced or metastatic breast cancer; and more key research that will be featured at the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast today. I am an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Megan Kruse, a breast medical oncologist and director of breast cancer research at the Cleveland Clinic Taussig Cancer Institute. We'll be discussing key abstracts in breast cancer that will be featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. Megan, it's great to have you back on the podcast. Dr. Megan Kruse: Thanks, Alison. Happy to be here. Dr. Allison Zibelli: So, let's begin with Abstract 505. This was another analysis of the SWOG S1007 (RxPONDER) trial, which was the trial that was looking at premenopausal women with intermediate risk oncotype scores. And do they benefit from chemotherapy? If you analyze the whole group, they do benefit from chemotherapy, but what this study questions is whether we can pull out the subset of these patients that actually benefit from chemotherapy? And what they tried doing was measuring various endocrine reproductive hormones and found that anti-mullerian hormone over 10 was the only one that predicted for chemotherapy benefit. What are your key takeaways from this study? Will it help us figure out who is truly postmenopausal biochemically? Dr. Megan Kruse: I think this is really promising. This is one of the toughest situations in clinic, honestly, when you have a premenopausal woman who has an intermediate oncotype risk. We know that chemotherapy is not going to make a huge difference potentially in their breast cancer outcomes, but it may add to some small differential benefit. I think that many of our patients are really afraid about leaving any impactful therapy on the table. And so, it'd be nice to have another marker to help sort out who in this group will really benefit. And the AMH levels, I think, are something that are very accessible for most practices, easily orderable. And it seems like this cutoff of 10 is a very well-known cut point in the AMH interpretation, and a pretty clear-cut point. So, I think it gives a little bit more objective view of who may actually benefit or not. When you look at the results shown in this abstract, for the women in the recurrence score less than 25 receiving chemotherapy followed by endocrine therapy, they had a benefit in five-year invasive disease-free survival of 7.8%. When you look at those oncotype reports and they suggest how much benefit you might get, that's right around the same number you see. So, I think that's supporting that this is the subgroup that's benefiting. When you look at those patients with AMH less than 10, they actually had a negative 1.7% difference in overall survival. So, you wonder, are we harming these patients by giving them chemotherapy? I think that's too far of a stretch to say. I wouldn't be worried about harm. But hopefully, we can stop giving chemotherapy to patients who truly are not going to benefit if we have an additional biomarker of response. That's what the promise is for this. So again, another potentially actionable abstract that we can put into practice pretty quickly. It's going to be hard to know how to use this, also in the context of the upcoming OFSET study or BR009, which is of course the study in the same group of premenopausal patients with node-negative or 1-3 lymph nodes involved, and intermediate oncotype scores, randomizing them to endocrine therapy with ovarian suppression versus chemoendocrine therapy. It would be kind of nice to see the AMH levels incorporated into that model to see if the same trend holds true. But I think we go back to the TAILORx and RxPONDER studies many times as good quality data, and the trend here is really striking. Dr. Allison Zibelli: I really like this study because one of the things I often struggle with in the clinic as a practicing breast oncologist is who's really in menopause. And we end up having these fights with the gynecologists where sometimes our opinions differ. And it would be really nice to have something this clear cut to say, “You're in biochemical menopause or you're not.” So, I look forward to seeing this used in a lot of different ways in the future. Dr. Megan Kruse: Yeah, I agree. And I think it's based on the other markers we have with estrogen levels, with FSH levels. If you're checking those sequentially in patients, we know they go up and down, and it's really hard to tell what we are capturing at this single point in time. And maybe that's what we're seeing in this analysis is that the AMH is a little bit more stable and reliable marker. So, I really love that. And I don't know about you, but in clinical practice it can be really hard. A lot of our patients have had uterine ablations or hysterectomies but have intact ovaries. And so, figuring out ovarian function status is actually much, much harder than it may seem superficially. Dr. Allison Zibelli: Okay, so let's focus on Abstract 513. I thought this was really interesting. It's a group of patients that we don't have much data for, and that's women that are ER-low, with an ER of 1% to 10% in early-stage breast cancer. Right now, national guidelines are sort of on the fence about whether these women benefit from endocrine therapy. So that's what this study tried to focus on. How will this study change how we approach this group of patients? Dr. Megan Kruse: This study really gave me pause and made me rethink what I'm doing on a day-to-day basis, because here, what the authors found in a very large NCDB analysis was that for women with ER-low status, so ER 1% to 10% positive, they actually did have benefit receiving endocrine therapy, it seems. What they found, after you adjust for many other confounding factors like age, comorbidity, and PR status, is that patients with ER-low breast cancer when they did not receive endocrine therapy actually had worse overall survival outcomes with a hazard ratio of around 1.2 to 1.3. This is a group where I have typically not pushed endocrine therapy very strongly. I think the patients, especially now, are receiving such intense therapy with chemoimmunotherapy in the preoperative setting, by the time they reach their adjuvant phase with immunotherapy, maybe with capecitabine, maybe with a PARP inhibitor, endocrine therapy seems, “Oh, why bother after we've done all of this?” And we know that the toxicities of endocrine therapy are real and can be very problematic. And so, I have often felt like it's the least important part of therapy and questioned whether we should even bother. But I think this analysis really challenges that and makes us think twice. And I think it speaks to a theme that we're seeing more and more about the heterogeneity of these breast cancer subtypes. And again, talking about clear-cut points in analysis, nothing is truly black and white. So maybe that little bit of expression does mean something. It does kind of stand in contrast to what we see in studies of ER-low behaving a bit more triple-negative like, but maybe they're their own category, and maybe it gives us a place to look for other therapy synergy in the future. But it certainly will make me stop and think again when I see a ER 4% patient. Should I talk to them about endocrine therapy? Dr. Allison Zibelli: Yeah, I totally agree with everything you said there. And we know that this is a biologically different group of patients than the ER strongly positive group, but maybe not as different as we once thought. Dr. Megan Kruse: Yeah. And I think there's still a lot of unknowns here about what if they're ER truly negative and PR a little bit positive. So, these clinical situations don't come up that frequently, but when they do, they're humbling, because I think we really, as much data as we have in breast cancer, it's pretty limited for these types of patients. Dr. Allison Zibelli: So, let's move on to Abstract 1003, which was a new combination in the INAVO120 trial. It was palbociclib plus fulvestrant with either inavolisib or placebo in patients with PIK3CA-mutated hormone receptor-positive, HER2-negative, locally advanced metastatic breast cancer in the second line, who relapsed within 12 months of adjuvant endocrine therapy completion. This is a big group of patients for us. Can you tell us about the study? And does this triple therapy, in your mind, represent a new standard of care? Dr. Megan Kruse: Yeah, this study was initially presented at our 2023 San Antonio Breast Cancer Symposium, and there I felt like it was a little bit of a surprise. There's been so much talk about PI3K-AKT-PTEN pathway impactful drugs and targetable mutations. We've heard a lot about alpelisib and capivasertib, and how these drugs are fitting into our practice. Then all of a sudden, we have this data with inavolisib that I wasn't really expecting to see. And perhaps I think one of the reasons that this study came about so suddenly, seemingly, and so quickly is because it looks at a really high-risk patient population. And so, these are those patients that are having relapses of their breast cancer within their initial, while on adjuvant AI therapy or within 12 months of stopping. And so, having a marker of this patient group that is developing, I think, early endocrine resistance and it's another space where it's kind of hard to identify who these patients are upfront. And so their response to therapy tends to be one of the best markers of risk moving forward. So, when this trial was originally presented, what was quite striking is that the progression-free survival was more than doubled for the triplet combination compared to the control arm. And those numbers were PFS of 15 months versus 7.3 months for the triplet versus the control. The response rate was also significantly improved, with the triplet going above 50%, versus a response rate in the control of about 25%. So, the results were really striking. But they clearly come with some caveats, which are that this is a very defined patient population of risk. Of course, they have to have the biomarker of a PIK3CA mutation, and in the control arm here, there was no PIK3-targeted medication. And so you wonder, are we just getting better results by including that more specific targeted therapy earlier on? It's hard to know, but I think that could certainly be a big part of this. And the other caveat, when I'm looking at the data, is how might we think about this in our real population? Because as we know, drugs that impact this pathway tend to have a lot of toxicity concerns, primarily hyperglycemia, diarrhea, and rash. And with this particular agent, there was also notable stomatitis, which is something we've seen with everolimus, of course, in this pathway, but not maybe as much with alpelisib and capivasertib. When you're thinking about all of those toxicities, keep in mind that this trial population included patients with a pretty tight fasting blood sugar requirement, A1c of less than 8, and not requiring insulin. So all of that being said, I think this combination seems really intriguing for efficacy. This is a patient population I'm worried about, because we know that these patients are likely not going to get the same upfront benefit of CDK4/6 inhibitor-based therapy, like maybe we see for a patient with long disease-free survival or de novo metastatic breast cancer. But I think it's going to have some meaningful issues in clinic regarding tolerability. And then, of course, the regimen is more complex. We're talking about two different oral agents and an intramuscular injection, which could be hard for some patients, and it's going to have some decent financial toxicity associated with it. So, I think it's really, really exciting and has the potential to make an impact in first-line therapy. But I don't envision it being the standard of care first-line therapy for everyone, particularly in light of some of the other data we have in the first line questioning, like from the SONIA trial, how important is CDK for everyone? Again, this is I think where we're starting to get subsets within subsets of this first-line patient population of who needs escalation of therapy and who may benefit from more de-intensified therapy. Dr. Allison Zibelli: I agree, these agents have significant toxicity, and especially financial toxicity is something that we at the academic setting frequently forget about because a lot of our patients are on trials. So, it will be interesting to figure out how we're going to use these agents in real life. So, for our final abstract, I wanted to discuss Abstract 10508, which was a prevention trial. I think pretty much everybody's patients are going to be asking them about this because it's about GLP-1 inhibitors. We know that bariatric surgery does prevent obesity-associated cancers. This study explored whether the GLP-1 agonists could offer a similar result to bariatric surgery in patients with BMIs over 35. What do you think about this study? Dr. Megan Kruse: I thought this was such an interesting and timely study and question. These drugs are out there – Ozempic, Mounjaros, and Wegovy – and our patients ask about them. And I think there has been a lot of interest for years now about the impact of lifestyle factors on cancer incidence, particularly in breast cancer, where we know that obesity does seem to be related to cancer incidence. And with all of our concerns about hormonal exposure and extra weight, extra adipose tissue being a source of potential extra estrogen, this is a really key topic. Talking about financial toxicity, again, I think that is honestly probably the bigger hurdle because this study does reinforce that patients who are receiving GLP-1 receptor antagonists and those who have had bariatric surgery do benefit in terms of cancer-related survival and all-cause related survival. So, I think the impact on metabolic factors is making a difference in cancer incidence and outcomes. But access and equity will be the big issue here, right? Dr. Allison Zibelli: Yes. Dr. Megan Kruse: Can we get patients on these drugs? I certainly have had patients with a history of breast cancer who have been on these medications, and they have done great with them in terms of weight loss. We know that our therapies, many times, do have the side effect of weight gain. So, I wonder if there is a part of weight management that maybe we haven't talked about so much as oncologists that we need to talk about moving forward and would be very welcome by our patients. But it'll have its own caveats, of course. Not only the financial issue but there's the durability issue. And I think when you look at the degree of impact of these medications versus bariatric surgery, you do see a greater impact from bariatric surgery, in not only the degree of weight loss but also the sustainability of that weight loss. So, I think for the right patient at the right time, bariatric surgery may still be the better option, but that's not going to be an option for a lot of patients. It is a huge shift in lifestyle and medications and many ways might be easier, so more to come. I also wonder about looking at this data through the lens of different cancer types. What will we find out? Is the trend for colon cancer going to be different from the trend for breast cancer? Will the trend within breast cancer be different for breast cancer subtypes? I would very much welcome more data in this space, and it is nice to see a first step forward. Dr. Allison Zibelli: I thought the most interesting thing about this study was that while bariatric surgery patients lost more weight, GLP-1 patients had a higher decrease in obesity-related cancer risk. So, it shows to me that there is something beyond just weight. It is something in metabolism that is driving these cancers. Dr. Megan Kruse: Yes, and I think that that goes back to some things we have thought about for a long time with insulin levels and insulin-like growth factor, and all of these things that I think when our patients look at more metabolic approaches to cancer control, this is probably what we are trying to get at. We have just never had great ways to measure it or influence it, and perhaps now we finally do. I would love to see some partnering work here in the future with oncologists and endocrinologists and digging into these patients who have great responses to see what we are actually seeing at the hormone level. Dr. Allison Zibelli: Well, thank you so much, Megan, for your great insights today on the ASCO Daily News Podcast. We really appreciate you coming to talk with us again. Dr. Megan Kruse: Thank you. It has been a great conversation. Thank you for opening my eyes to these abstracts, and I am happy to see what else ASCO brings. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find links to all the abstracts we discussed today in the transcript of this episode. Finally, if you value the insights you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people find us. Thank you for listening. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Allison Zibelli Dr. Megan Kruse @MeganKruseMD Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Allison Zibelli: None Disclosed Dr. Megan Kruse: Consulting or Advisory Role: Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, Lilly
Featuring perspectives from Dr Seth Wander, including the following topics: Case: A woman in her mid-50s with ER-positive, PR-negative, HER2 IHC 1+ metastatic breast cancer (mBC), Recurrence Score® (RS) = 35 (0:00) Mechanisms of resistance to antiestrogen therapy in HR-positive mBC (2:33) Optimal approaches to biomarker assessment (15:37) Case (continued): A woman in her mid-50s with ER-positive, PR-negative, HER2 IHC 1+ mBC, RS = 35 (18:27) Case: A woman in her early 60s with de novo HR-positive, HER2-negative mBC with an ESR1 mutation after disease progression on first-line ribociclib/letrozole (20:22) EMERALD — Phase III data guiding the use of elacestrant (21:39) Emerging oral selective estrogen receptor degraders — camizestrant and imlunestrant (29:32) Case (continued): A woman in her early 60s with de novo HR-positive, HER2-negative mBC with an ESR1 mutation after disease progression on first-line ribociclib/letrozole (45:44) Case: A woman in her early 60s with HR-positive, HER2-negative mBC and a PIK3CA mutation who develops a new ESR1 mutation after disease progression on CDK4/6i and aromatase inhibitor (47:22) CAPItello-291 — Phase III data guiding the use of capivasertib (48:52) Case (continued): A woman in her early 60s with HR-positive, HER2-negative mBC and a PIK3CA mutation who develops a new ESR1 mutation after disease progression on CDK4/6i and aromatase inhibitor (52:41) Additional promising antiestrogens — vepdegestrant and lasofoxifene (58:41) CME information and select publications
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 discussion with Dr. Hope Rugo, we covered her study Capitello-291, which led to the approval of Capivasertib in hormone receptor-positive breast cancer with AKT1, PTEN, and PIK3CA mutations, which are seen in 40-50% of the cases. We touched base on sequencing of this therapy, and important clinical pearls around the side effect management associated with this drug.
Welcome back to another episode of Breast Cancer Conversations, where we continue to share valuable insights from the San Antonio Breast Cancer Symposium. As a breast cancer survivor and the founder of survivingbreastcancer.org, I'm thrilled to bring you key takeaways from one of the world's largest breast cancer conferences.In this episode, we focus on what to do when CDK4-6 inhibitors, such as Ibrance, Kisqali, and Verzenio, stop working. Our guest, Amy Bremer, highlights the importance of getting a biopsy to check for mutations, which can be done through a liquid biopsy or a tissue biopsy. This step is crucial for determining the next course of action.We delve into the various treatment options available based on specific mutations. For instance, if your cancer has a PIK3CA mutation, a combination of PIQRAY and Faslodex might be recommended. Other drugs like Trucap, Orserdo, and LSS strontosome are also discussed as potential options for different mutations.For those without mutations, there are still choices available, such as Affinitor plus Faslodex, or considering a switch to a different CDK4-6 inhibitor. We also discuss the possibility of continuing treatment beyond progression or, in cases of aggressive progression, looking into chemotherapy or antibody drug conjugates (ADCs).Stay tuned for our next episode, "on SERDs, SERMs, CERANs, and PROTACs" and remember to subscribe to Breast Cancer Conversations. Please note that our podcast shares personal experiences and is not a substitute for professional medical advice. If you have specific topics in mind or want to be a guest, feel free to reach out to me.Thank you for listening, and let's continue to empower each other through community, education, and resources.00:02:44 - Topic: CDK4-6 Inhibitor Efficacy00:03:31 - Options After Endocrine Therapy and CDK4-6 Inhibitors00:04:35 - Treatment Options Based on Specific Mutations00:05:40 - Options Without Identified Mutations00:06:43 - Inherited Mutations and Treatment Choices00:07:09 - Expert Opinions on Treatment Complexity00:08:44 - Importance of Clinical Trials+++++++++++++++++++++Attend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramLaura and Will: https://www.instagram.com/laura_and_will/SurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the show
Recently, the FDA granted approval to capivasertib in combination with fulvestrant for patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations. In this interview, Editorial Board member Dr. Jason Mouabbi speaks with Dr. Carlos Doti, Head of Medical Affairs, US Oncology at AstraZeneca, about the significance of the approval, its dosing schedule, AstraZeneca's approach towards patient education and adverse event management, and the future of capivasertib in different treatment settings.
Dr. Banu Arun and Dr. Sana Al Sukhun share recommendations from the newest ASCO resource-stratified guideline on systemic treatment for patients with metastatic breast cancer. They describe the importance of this new guideline, the four-tier resource setting approach, key recommendations, and implementation considerations. Recommendations are discussed for systemic therapy for HER2-positive, triple-negative, and hormone receptor-positive metastatic breast cancer, across Basic, Limited, and Enhanced resource settings. Drs. Arun and Al Sukhun highlight the importance of this guideline for clinicians and patients in regions with limited resources to optimize cancer care. Read the full guideline “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline” at www.asco.org/resource-stratified-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/resource-stratified-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the JCO Global Oncology, https://ascopubs.org/doi/10.1200/GO.23.00285 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Banu Arun from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Sana Al Sukhun from Al Hayat Oncology Practice in Amman, Jordan, co-chairs on “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.” Thank you for being here, Dr. Arun and Dr. Al Sukhun. Dr. Banu Arun: Thank you for having us. Dr. Sana Al Sukhun: Thank you. Pleasure to join you. Brittany Harvey: And before we discuss this guideline, I'd just 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 the guests who have joined us today on this episode, are available online with the publication of the guideline in the JCO Global Oncology, which is linked in the show notes. Then, to jump into the content of this guideline, Dr. Al Sukhun, can you first provide an overview of the scope and the purpose of this guideline? Dr. Sana Al Sukhun: Sure. And again, thank you, Brittany. Pleasure to join you. This guideline is really interesting and very important. It addresses the care and treatment of the most common cancer worldwide, particularly metastatic breast cancer, taking into consideration different availability of resources, particularly in countries with limited resources. As you know, most of us are aware of the importance of clinical practice guidelines improving outcomes for patients in medicine, not only in oncology, but most of those guidelines are developed in countries that are highly resourced. So their applicability in countries of limited resources that lack infrastructure and resources is definitely limited because they cannot really adopt and adapt to those guidelines, which makes resource adapted or resource stratified guidelines quite important and helpful. First, to clinicians caring for patients so that they can properly allocate resources, prioritize how to use therapy for patients, but also even policymakers to allocate resources and plan graduated implementation of science to improve outcomes for their patients according to the progressive availability of resources. So we're talking about breast cancer, the most common cancer worldwide. And not only is it the most common cancer worldwide, but also more than two-thirds of new cases are diagnosed in countries of limited resources. Unfortunately, they also carry the burden of more than 70% of the mortality attributed to breast cancer. Another challenge is that the median age for the patients affected with breast cancer in countries of limited resources is indeed at least a decade younger than Western societies, which adds to the burden, not only the social, but also the economic burden of cancer. And unfortunately, presentation in these countries is mostly locally advanced, metastatic breast cancer, therefore comes the focus on helping our colleagues in countries of limited resources to care for patients according to the resources available, not only in countries of limited resources, even colleagues practicing in less fortunate areas within countries that are highly resourced. Brittany Harvey: Excellent. Thank you for providing that background information for this guideline. So then you've just described how many countries and areas have different resources. So, Dr. Arun, could you describe the four-tier resource setting approach that this expert panel used? Dr. Banu Arun: Yeah, Brittany, that's a good question. I think it's important to know where we started and what infrastructure we used. So for developing resource stratified guidelines, ASCO has adopted its framework from the four-tier resource setting approach, which was actually developed by the Breast Health Global Initiative, and we employed modifications to that framework based on the disease control priorities. What this framework emphasizes is also that variations can be present not only between countries, but actually within countries with disparities, for example, differences between rural and urban areas within one country. So the four settings are obviously basic, limited, enhanced, and maximal settings. The basic setting includes core resources or fundamental services that are really absolutely necessary for any public health, primary health care system to function at all. These include services that are typically applied in a single clinical interaction. For example, vaccination is feasible for highest need populations. The next tier would be the limited setting. That includes countries or settings with second-tier resources or services that are intended to produce major improvements in outcomes, such as incidences and cost effectiveness. Unlike the basic setting, it can involve single or multiple interactions with providers or healthcare services. Then the third tier is the enhanced setting, where the services are optional but important, and these services should ideally produce further improvements in outcome and increase the number of quality of options and also individual choices, maybe countries having the ability to track patients and links to registries. And then the last one is of course, the maximal setting that includes high-level, state-of-art resources and services that are available in some high-resource countries. Brittany Harvey: Thank you for describing that framework and the approach that the panel used. So then I'd like to move on and talk about the key high-level recommendations of this guideline for systemic therapy for metastatic breast cancer across those three lower tiered resource settings - the basic, limited, and enhanced resource settings. So, Dr. Al Sukhun, could you start with the recommendations across these settings focusing on HER2-positive breast cancer? Dr. Sana Al Sukhun: Sure. You know, HER2-positive metastatic breast cancer is one of the most aggressive subtypes of breast cancer. However, its outcome has been transformed with the introduction of HER2-targeted therapy. So, apart from patients who suffer from congestive heart failure or limited compromised ejection fraction, which can be evaluated on a case-by-case basis, patients are candidates for HER2 targeted therapy. When we made the recommendations according to the availability of resources, we started in a gradual approach. So, in a maximal setting, you treat patients with HER2-positive metastatic breast cancer in the frontline setting using the combination of trastuzumab, pertuzumab, and taxanes or endocrine therapy if patients have limited disease burden, or if they have the recurrence after a long disease-free interval. Usually, the combination of trastuzumab and pertuzumab with taxane is used. But then again, clinicians can use navelbine, considering good data from the HERNATA trial about its efficacy as compared to taxanes and even also, we recommended platinum therapy according to availability. However, if pertuzumab is not available, you go to the next level where we recommend offering, again, chemotherapy, be it taxane, navelbine, platinum, with trastuzumab, or even without trastuzumab if trastuzumab is not available. So, something to keep in mind, chemotherapy is not without efficacy in this aggressive subtype. It is not as good as when you use the combination with HER2-targeted therapy, but it still works. Patients and clinicians in this era of biologic therapy immunotherapy tend to think only pricey medications are the ones that can be used for treatment and improving outcome. However, definitely adding help with targeted therapy is great whenever it's available. But if it's not available, chemotherapy still could be used in a sequential manner. We listed all possible chemotherapeutic options starting with taxanes, navelbine, platinums, even CMF, capecitabine. When it comes to second-line therapy, including those patients who relapse within 12 months of adjuvant therapy, the optimal line of treatment would be trastuzumab deruxtecan. However, if it's not available, we recommend to be offered with successive or progressive preference, if it's not available, T-DM1 could be used. If it's not available, capecitabine and lapatinib could be used. If it's not available, trastuzumab with chemotherapy could be used. If it's not available, we go back to the sequential use of chemotherapy, including adriamycin, taxanes, platinums, capecitabine, or even CMF. Brittany Harvey: I appreciate you reviewing those recommendations for HER2-positive breast cancer. So then, moving along, Dr. Arun, what are the recommendations for patients with metastatic triple-negative breast cancer? Dr. Banu Arun: Thank you, Brittany. Triple-negative breast cancer, of course, is one of the serious subgroups of breast cancer. About 10 to 15% of patients have triple-negative breast cancer. What I will do is I will divide it into the three-tier settings as well as first-, second-, and third-line therapies. For patients with triple-negative PD-L-negative metastatic breast cancer in the limited settings and even enhanced settings, single-agent chemotherapy rather than combination chemotherapy should be recommended as the first-line. However, if patients are symptomatic or have immediate life-threatening disease, combination chemotherapy can be offered. For patients with triple-negative breast cancer that are PD-L1 positive, they may be offered in addition to chemotherapy, an immune checkpoint inhibitor, as first-line therapy, most probably in enhanced settings and in basic and limited, of course, chemotherapy. When you move on to the second-line for metastatic breast cancer in patients with or without previous PD-L1 checkpoint inhibitors, clinicians can offer palliative or best supportive care in the basic setting. In the limited setting, chemotherapy with anthracyclines, taxanes, platinums are options. And in the enhanced setting if sacituzumab govitecan is not available, chemotherapy would be an option. Now, when we move on to the third-line setting for triple-negative breast cancer, clinicians can actually offer chemotherapy and/or palliative care, depending really on the status of the patient. Brittany Harvey: Excellent. Thank you for providing those recommendations for triple-negative breast cancer. As you mentioned, it's one of the rarer forms of breast cancer. So then, Dr. Al Sukhun, I'd like to move into the last section of patients, actually the most common, but hormone receptor-positive breast cancer. What are those recommendations? Dr. Sana Al Sukhun: Thank you, Brittany. As you mentioned, it's the most common subtype worldwide. The rule of the thumb is sequential hormonal therapy, depending on availability. So, whatever you have hormonal therapy, sequential hormonal therapy unless pending visceral crisis or symptomatic disease, it's recommended that you offer sequential single-agent chemotherapy, unless it's a real visceral crisis, where we recommend combination chemotherapy. That's a classic in all our guidelines. When considering frontline hormonal therapy, again, I will start from the maximal level and gradually recommend according to availability. So in enhanced levels in many countries now, we have generic CDK4/6 inhibitors, which increase their availability. So we do recommend hormonal therapy with CDK4/6 inhibitors. Upon progression or when they are not available, on progression, you move to the second line of hormonal therapy. If you have liquid biopsy, check for PIK3CA mutation. Sometimes you do have the liquid biopsy, but you do not have alpelisib to offer to your patients with hormonal therapy, then it's okay, you still can move to second-line fulvestrant with everolimus. Sequentially, you can move forward to fulvestrant by itself if you do not have everolimus. And even you can sequence tamoxifen until your patient stops responding to hormonal therapy then you can offer sequential single-agent chemotherapy. Brittany Harvey: Thank you, Dr. Al Sukhun for providing those recommendations. So then, Dr. Arun, what should clinicians do when we do not have access to receptor assessment? What is recommended for best practices for management of those patients? Dr. Banu Arun: So, Brittany, that's an important question. There are some basic settings where unfortunately, immunohistochemistry for ER/PR HER2neu determination is not available. Our group really recommends in these cases that clinicians may presume hormonal receptor positivity and offer tamoxifen in most cases. It is expected that IHC would be available in limited and, of course, enhanced settings. Brittany Harvey: Great. Thank you for providing that information. So further, what else should clinicians know as they implement these recommendations, Dr. Arun? Dr. Banu Arun: It's very important that we, all healthcare provider clinicians, really know the data. I think reading the guidelines or knowing about first and second line therapies is obviously important, but the devil is in the details. And I think knowing the publications and subgroup analyses, if needed, because every patient is different and sometimes the recommendations cannot go by the books. You really need to do an assessment of the patient and see in which setting you are and then make the most of the guidelines that are recommended. It's to guide. The name is guidelines. It's to guide. And ultimately, it's the clinician's responsibility to find the best available therapy for the patient. And sometimes that includes no treatment and supportive care. Dr. Sana Al Sukhun: Totally agree with Dr. Arun. They are there to support the clinician decision. After all, the clinician is the one who sees the patient, who can evaluate the patient from all aspects — social aspect, physical aspect, the tumor aspect. So it's not just about the tumor, it's about the patient and the environment where the clinician is treating the patient. However, I believe there is support to the clinician not only in treating the patient, but also on addressing priorities for research to improve outcomes for patients in different resource settings. There is also support for the clinicians to help them advocate for improving care for patients in a strategic way, where they prioritize resource allocation. So they are there to support the clinician at all levels, not only when treating patients, but when advocating for patients, when helping patients to make decisions, when they're discussing with their health officials and policymakers. Brittany Harvey: Absolutely. Those are excellent points that you both made about individualizing patient care for the specific person in front of you. So then, finally, Dr. Al Sukhun, how will these guideline recommendations impact patients with metastatic breast cancer globally? Dr. Sana Al Sukhun: The ultimate goal for anything we do, including guidelines, is to improve outcomes for patients worldwide. They are there to support clinician decisions, empower clinicians to optimize care for their patients, to advocate for improving outcomes for patients by strategically allocating resources according to the most impactful strategy. They help clinicians to identify areas for research that are needed according to the resources available to them. They are there to guide policymakers, again, also implementing strategies to implement science that could improve outcomes in an efficient way for their societies. So hopefully, all these, with our research, with our advocacy, with our health policy, with our treatment decisions, hopefully all these will improve outcomes for breast cancer patients and ultimately reduce mortality, particularly in less fortunate, limited resource settings for patients everywhere. Brittany Harvey: Absolutely. We hope that these guidelines improve outcomes and quality of life for patients worldwide. So I want to thank you both so much for your work to develop this guideline. There's certainly a large amount of recommendations, so I encourage our listeners to read the full guideline, which is linked in the show notes. And I want to thank you so much for your time today, Dr. Al Sukhun and Dr. Arun. Dr. Sana Al Sukhun: Thank you for having us. Dr. Banu Arun: Thank you, Brittany. Brittany Harvey: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/resource-stratified-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've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In discussion with Dr. Hope Rugo, covering the San Antonio Breast Cancer Symposium 2023 Highlights from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Rugo: - NATALEE Update – Ribociclib + Nonsteroidal AI as Adj Treatment in Patients with HR+/HER2− Early Breast Cancer: Final iDFS analysis - MONARCH 3 – Final OS Results of Abemaciclib Plus a Nonsteroidal AI as First-line Therapy for HR+, HER2– Advanced Breast Cancer - INAVO120 – Phase III Study of Inavolisib or Placebo in Combination with Palbociclib and Fulvestrant in Patients with PIK3CA-mut, HR+, HER2– Locally Adv/Metastatic Breast Cancer - TROPION-Breast01 – Phase III Study of Dato-DXd vs Chemo for Patients with Previously Treated Inoperable/Metastatic HR+, HER2– Breast Cancer
Dr Gradishar discusses the FDA approval of capivasertib plus fulvestrant for patients with advanced HR-positive, HER2-negative breast cancer harboring PIK3CA, AKT1, or PTEN alterations.
San Antonio Breast Cancer Symposium is here, and this year, OFTIM (Oncology for the Inquisitive Mind) is bringing you the latest and greatest in all things breast cancer. With over 10000 attendees, the research and vibrant discussions did not disappoint, with updates, controversies and complexities. Taking centre stage were PIK3CA mutation treatments, updates on CDK4/6 inhibitors and the age-old question - does exercise improve outcomes for our patients?Studies discussed in today's episode (subscription may be required)MONARCH-3KATHERINEINAVO120PREFERABLE EFFECTFor 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 Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.
Guest: Megan Kruse, MD While intrinsic mutations, like PIK3CA, are present at the outset and can be identified upfront in patients with HR+/HER2- metastatic breast cancer, acquired mutations, like ESR1, cannot be detected on baseline tumor profiling. That's why longitudinal monitoring with liquid biopsies over the course of treatment is required. Learn more about these key differences in testing for acquired versus intrinsic mutations with Dr. Megan Kruse, a breast medical oncologist at the Cleveland Clinic.
Dr. Angie DeMichele and Dr. Lynn Henry present the latest rapid recommendation impacting two ASCO guidelines. This update focuses on testing for ESR1 mutations in patients with hormone receptor-positive, HER2-negative metastatic breast cancer, and presents treatment recommendations for patients with a detectable ESR1 mutation. Dr. DeMichele and Dr. Henry review the recent data from the EMERALD trial, discuss it's implications for practice, and ongoing developments they're monitoring for more effective therapeutic options. Read the latest update, "Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation 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 update and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.2300638 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Angie DeMichele from University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, authors on ‘Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update'. Thank you for being here, Dr. DeMichele and Dr. Henry. Dr. Angie DeMichele: It's a pleasure. Dr. Lynn Henry: Thank you. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this podcast episode today, are available online with a publication of the rapid recommendation update in the Journal of Clinical Oncology, which is linked in the show notes. So then, getting into the content of this rapid recommendation first, Dr. Henry, what prompted this rapid update, which provides updated recommendations for two ASCO guidelines? First, the ‘Biomarkers for Systemic Therapy and Metastatic Breast Cancer Guideline', last published in 2022, and the ‘Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Guideline', which was last updated in 2021. Dr. Lynn Henry: Thank you, Brittany. There's been a lot of exciting news for the treatment of metastatic breast cancer in the last few years. This particular update reflects the results of the phase III EMERALD trial. This trial compared the new oral selective estrogen receptor degrader, elacestrant, to standard-of-care endocrine therapy with either fulvestrant or an aromatase inhibitor in patients with hormone receptor-positive, HER2-negative metastatic breast cancer that had previously progressed during treatment with a CDK4/6 inhibitor in combination with endocrine therapy. Compared to standard-of-care, in this trial, they showed improved progression-free survival in both the overall study population as well as specifically in the patients who had a detectable ESR1 mutation in their circulating tumor DNA. These findings were published in the Journal of Clinical Oncology in 2022, and the drug was subsequently approved by the US Food and Drug Administration in January 2023. Therefore, we felt that it was important to update the guidelines to reflect the results of this trial and the new drug approval. Brittany Harvey: Excellent. Thank you for describing the results of that trial and the new approval. So then, based on this data, Dr. DeMichele, what is the updated recommendation from the guideline expert panel for testing for ESR1 mutations? Dr. Angie DeMichele: So, the guideline panel has now recommended that ESR1 mutation testing occur for any patient who develops a recurrence or progression on endocrine therapy. And this is specifically in reference to the development of ESR1 mutations that can occur after a patient has been exposed to aromatase inhibitors. The guideline itself recommends that this testing be done on either tumor or blood, but blood is preferable because there is increased sensitivity using ctDNA testing over tumor testing. So this was an important component of the change in the recommendation because it's linked to the approval of elacestrant as a therapy. Patients are only eligible to receive elacestrant if they harbor an ESR1 mutation. Brittany Harvey: Understood. I appreciate that explanation. So then, Dr. Henry, following that recommendation for testing, what is the new recommendation for treatment for patients with a detectable ESR1 mutation? Dr. Lynn Henry: Yes. So patients who have a detectable ESR1 mutation and who have previously received treatment with endocrine therapy in combination with the CDK4/6 inhibitor for advanced breast cancer now have multiple treatment options. The newest option is this new drug, elacestrant, which is given 345 milligrams orally daily. There are still the other options that we already knew about, which include a different endocrine therapy alone, such as fulvestrant or an aromatase inhibitor, or possibly an endocrine therapy in combination with a targeted agent, such as alpelisib or everolimus. And those decisions really need to be based on what other mutations are present in the patient's cancer. Importantly, at this time, there are no safety or efficacy data to support using elacestrant in combination with targeted agents. Therefore, to date, it has only been approved to be used as monotherapy. But really, this is an exciting new potential option for treatment for patients whose tumors have a detectable ESR1 mutation. Brittany Harvey: Yes, this is an exciting option, and I appreciate you describing how this fits in with the existing treatment paradigm for these patients. So then, Dr. DeMichele, as these new recommendations are implemented, what should clinicians know? Dr. Angie DeMichele: I think this is a really important new step in breast cancer in testing for ESR1 mutations. We've not previously had a medication that required the existence of an ESR1 mutation for patients to be eligible for therapy. So obtaining ESR1 mutation testing may be new for some clinicians. As I stated earlier, this can be done either on a tumor biopsy or on blood testing using the Guardant360 ctDNA test, which is the test that was used in the clinical trial. And it was stated that the ctDNA test is more sensitive than the tumor test. But what's really important here is that the testing occur at the time that the clinician is considering switching therapies, because it's important to find that ESR1 mutation prior to starting the next therapy. ESR1 mutations don't typically exist in a tumor at the time it's diagnosed. They only emerge over time after patients have been exposed to different endocrine therapies, particularly aromatase inhibitors. It's also possible that at the time of a recurrence after aromatase inhibitor therapy or progression on an aromatase inhibitor, there will not be any detectable ESR1 mutation. However, with subsequent therapy, an ESR1 mutation can occur. So a patient may need serial testing over time to determine whether an ESR1 mutation has developed. Brittany Harvey: Understood. Those are important clinical implications. So then, Dr. Henry, Dr. DeMichele just described some of the testing implications for patients. But in your view, how does this rapid update impact patients with hormone receptor-positive, HER2-negative metastatic breast cancer? Dr. Lynn Henry: So as Dr. DeMichele mentioned, this update specifically highlights approval of a new drug, oral SERD elacestrant. This is an exciting new option for treatment of patients whose tumors have an ESR1 mutation. So previous data have demonstrated that cancers with ESR1 mutations do not respond as well to previously available standard-of-care treatments such as aromatase inhibitors. It's nice to have a drug that may be a better option than some of the previously existing treatments for hormone receptor-positive, HER2-negative metastatic breast cancer. Brittany Harvey: Definitely. That's great to hear. So then, finally, Dr. DeMichele, are there ongoing research developments that the panel is monitoring for future updates to these guidelines? Dr. Angie DeMichele: We certainly are monitoring additional research developments, Brittany. Specifically, there are numerous other selective estrogen receptor degraders that are being tested, and these also may ultimately require ESR1 mutation testing and detection for therapies. So we'll be monitoring the results of those clinical trials. We'll also be watching for additional trials that help us understand how to best utilize elacestrant and whether it can be combined with other therapies. And then, finally, I think we have to think about how to place this in the context of other types of molecular changes that we may detect in metastatic breast cancer, such as PIK3CA mutations and others. And as we move forward, I anticipate that we will have additional therapies that are specifically targeted to molecular changes in the tumor. And I think this is a really exciting development because this is a major step forward toward precision medicine, where we're really tailoring the therapy to the specific biology of the patient's tumor and actually responding to the ways in which the tumor is evolving over time and in response to treatment. So as tumors become increasingly resistant to therapies, we can actually take advantage of those resistance mechanisms to develop therapies that will be more effective. Brittany Harvey: Yes, we'll look forward to those new therapies and research developments and then updated guidelines in the future. So I want to thank you both so much for your work on this rapid recommendation update and for your time today, Dr. DeMichele and Dr. Henry. Dr. Angie DeMichele: Thank you. Dr. Lynn Henry: Thank you very much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guidelines, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the newly redesigned ASCO Guidelines app, available for free in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this Podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Featuring perspectives from Drs Aditya Bardia, Matthew Goetz, Virginia Kaklamani, Kevin Kalinsky and Hope Rugo, including the following topics: Current Role of Genomic Assays for Hormone Receptor (HR)-Positive Localized Breast Cancer Introduction (0:00) Case: A premenopausal woman in her early 40s with 9-mm, Grade III, ER/PR-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) – 21-gene Recurrence Score® 22 — Alan B Astrow, MD (3:39) Case: A premenopausal woman in her mid 30s with 3.6-cm, ER/PR-positive, HER2-low (IHC 1+), sentinel node-positive (4/4) multifocal IDC after bilateral mastectomies, adjuvant AC-T and ovarian function suppression (OFS)/aromatase inhibitor, Ki67 50% — Laila Agrawal, MD (9:40) Dr Goetz presentation (19:43) Optimizing the Management of Localized ER-Positive Breast Cancer Case: A woman in her early 40s with 5.5-cm, ER/PR-positive, HER2-negative, node-positive (20/21) IDC after bilateral mastectomies, bilateral salpingo-oophorectomy, adjuvant AC-T and initiation of letrozole/abemaciclib, Ki-67 3% — Susmitha Apuri, MD (32:22) Case: A woman in her mid 50s with de novo ER-positive, PR-negative, HER2-negative ulcerated breast cancer with pulmonary and extensive spinal metastases — Jennifer L Dallas, MD (40:45) Dr Kaklamani presentation (45:32) Selection and Sequencing of Therapy for Patients with ER-Positive Metastatic Breast Cancer (mBC) Case: A woman in her early 50s with ER/PR-positive, HER2-low mBC with a PI3KCA mutation who experiences a dramatic response to rechallenge with fulvestrant and a CDK4/6i (abemaciclib); now with progression and cytopenias — Kapisthalam (KS) Kumar, MD (59:07) Dr Kalinsky presentation (1:09:53) Recent Appreciation of HER2 Low as a Unique Subset of HR-Positive Breast Cancer Case: A premenopausal woman in her late 30s with ER/PR-positive, HER2-low (IHC 1+) IDC after adjuvant tamoxifen and OFS x 5 years, now with bone and liver metastases — Dr Agrawal (1:19:45) Dr Bardia presentation (1:24:29) Novel Strategies Under Investigation for Patients with HR-Positive mBC Case: A woman in her early 90s with ER/PR-positive, HER2-low (IHC 1+) mBC and progressive disease on multiple lines of endocrine and chemotherapy receives T-DXd — Dr Astrow (1:38:44) Case: A woman in her mid 40s with ER/PR-positive, HER2-low (IHC 2+) mBC who has received fulvestrant/abemaciclib, now receiving exemestane/everolimus – ESR1 and PIK3CA mutations — Dr Dallas (1:44:15) Dr Rugo presentation (1:49:58) CME information and select publications
Featuring perspectives from Drs Erika Hamilton, Sara Hurvitz, Ian Krop, Shanu Modi and Sara Tolaney, including the following topics: Optimizing the Management of Localized HER2-Positive Breast Cancer Introduction (0:00) Case: A woman in her mid 60s with pulmonary hypertension and triple-positive, node-positive infiltrating ductal carcinoma (IDC) after neoadjuvant TCHP and clinical complete remission — Susmitha Apuri, MD (4:31) Case: A woman in her early 60s with a 1.7-cm, triple-positive, clinically node-negative IDC — Ranju Gupta, MD (10:05) Dr Tolaney presentation (18:44) Current Considerations in the Treatment of HER2-Positive Metastatic Breast Cancer (mBC) Case: A woman in her early 60s with an 8-cm, ER-negative, PR-positive, HER2-positive IDC and positive nodes bilaterally after neoadjuvant TCHP and bilateral mastectomies with no residual disease — Henna Malik, MD (31:12) Case: A woman in her late 50s with Stage IIIA, ER/PR-negative, HER2-positive, node-positive IDC with residual disease after neoadjuvant TCHP and mastectomy — Laila Agrawal, MD ()35:29 Dr Krop presentation (42:56) Management of HER2-Positive Breast Cancer with CNS Metastases Case: A woman in her early 90s with “mild” dementia and ER/PR-negative, HER2 IHC 1+ IDC with symptomatic chest wall recurrence after neoadjuvant paclitaxel/trastuzumab and lumpectomy — Alan B Astrow, MD (54:54) Case: A woman in her late 40s with a triple-positive multifocal IDC with a gBRCA2 mutation and HER2-negative axillary nodes after neoadjuvant TCHP and bilateral mastectomies with significant response in the breast but 49 positive nodes — Zanetta S Lamar, MD (1:00:01) Dr Hamilton presentation (1:06:51) Recent Appreciation of HER2 Low as a Unique Disease Subset; Future Directions in the Management of HER2-Positive and HER2-Low Breast Cancer Cases: A premenopausal woman in her late 30s with a triple-positive IDC who develops brain metastases while receiving THP; A woman in her late 60s with an ER/PR-negative, HER2-positive IDC who develops brain metastases after first-line THP and second-line T-DM1 — Kelly Yap, MD & Rohit Gosain, MD (1:20:46) Case: A woman in her mid 60s with ER/PR-negative, HER2-positive mBC treated with paclitaxel/trastuzumab, then T-DXd on progression — Joanna Metzner-Sadurski, MD (1:29:40) Dr Modi presentation (1:40:51) Incidence and Management of Adverse Events Associated with HER2-Targeted Therapy Case: A woman in her early 60s with recurrent triple-positive mBC whose disease converts to HER2-negative, PIK3CA-positive at the time of progression — Dhatri Kodali, MD (2:01:10) Dr Hurvitz presentation (2:05:08) CME information and select publications
Guillaume Canaud, MD, PhD, of the Paris Descartes University, explains why it is important to regularly measure objective outcomes in persons with PiK3CA-related overgrowth syndrome (PROS).PROS is a group of rare congenital disorders that lead to the overgrowth of parts of the body. PROS is caused by gain of function mutations in the PIK3CA gene. Specific disorders under the umbrella of PROS include fibroadipose hyperplasia, hemihyperplasia multiple lipomatosis (HHML), CLOVES syndrome, macrodactyly, fibroadipose infiltrating lipomatosis, megalencephaly-capillary malformation (MCAP), and dysplastic megalencephaly (DMEG).
Scientific Sense ® by Gill Eapen: Prof Trey Ideker is Professor of Medicine, Bioengineering and Computer Science at the University of California, San Diego. He directs the National Resource for Network Biology, and the Cancer Cell Map and Psychiatric Cell Map Initiatives. A multi-scale map of cell structure fusing protein images and interactions. Nature. 2021 Nov 24. doi: 10.1038/s41586-021-04115 “We Might Not Know Half of What's in Our Cells, New AI Technique Reveals Interpretation of cancer mutations using a multiscale map of protein systems. Science. 2021 A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. A protein interaction landscape of breast cancer. Science. 2021 Oct;374(6563):eabf3066 “Studies Delve Deep into the Protein Machinery of Cancer Cells.” NCI (4 Nov 2021) “From COVID to cancer, gene-mapping tool could ‘revolutionize' treatment“. SF Chronicle (2 Oc “Moonshot Project Aims to Understand and Beat Cancer Using Protein Maps“. Singularity Hub (5 Oct 2021) “Looking Beyond DNA to See Cancer with New Clarity,” Predicting Drug Response and Synergy Using a Deep Learning Model of Human Cancer Cells. Cancer Cell (2020), https://doi.org/10.1016/j.ccell.2020.09.014. PMID: 33096023. [PDF] [PubMed] Related Press: UCSD Health, AZoLifeSciences, Med India, Health IT Analytics and ScienceDaily. Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Systems. 2020 Aug 26;11(2):176-185.e6. doi: 10.1016/j.cels.2020.06.006. Epub 2020 Jul 2. PMID: 32619550 [PDF] [PubMed] *Cover Article Related Press: Here's a better way to convert dog years to human years, scientists say. Science Magazine (15 Nov 2019). See also: Scientific American, BBC, NPR, Washington Post, Discover Magazine, Smithsonian, New York Post, (and more) Identifying Epistasis in Cancer Genomes: A Delicate Affair. Cell. 2019 May 30;177(6):1375-1383. doi: 10.1016/j.cell.2019.05.005. Review. PMID: 31150618 [PDF] [PubMed] Using deep learning to model the hierarchical structure and function of a cell.* Nat Methods. 2018 Mar 5. doi: 10.1038/nmeth.4627. PMID: 29505029 [PDF] [PubMed] [Cover Art] *Cover article Please subscribe to this channel: https://www.youtube.com/c/ScientificSense?sub_confirmation=1 --- Send in a voice message: https://anchor.fm/scientificsense/message Support this podcast: https://anchor.fm/scientificsense/support
(00:32) Could you provide a little bit of background about yourself, please?(01:01) Please give us a brief overview of the new PIK3CA assay. (02:09) Why do we offer two different tests, and when should each be ordered?(03:58) Which patients should have this testing?(04:39) Is this testing used for patients being considered for second-line treatment after first-line hormone receptor treatment?(05:20) Is there anything else you would like to add about the PIK3CA testing?(06:23) Why is it important to know the molecular signature of these tumors?
CME credits: 0.50 Valid until: 25-08-2023 Claim your CME credit at https://reachmd.com/programs/cme/evolving-perspectives-in-pik3ca-related-overgrowth-spectrum-diagnosis-treatment/13790/ PIK3CA-related overgrowth spectrum (PROS) refers to various clinical entities that share the same pathogenetic mechanism. These disorders are caused by somatic gain-of-function PIK3CA mutations. Diagnosis of PROS is often challenging and requires DNA sequencing of the affected tissue. PIK3CA genetic mutations vary greatly depending on the tissue being tested. PROS is not considered an inherited disease. The road to a diagnosis of a rare disease can be a long, winding process. Because of its rarity, a wide spectrum of symptoms, and disease heterogeneity, patients may feel alone and as though they are the only ones with the disease. Management of PROS currently involves symptomatic treatment of its manifestations; an unmet need exists for targeted, systemic therapies. Currently, there is no cure for PROS. This educational activity will assist the interprofessional care team to better understand, apply, and interpret advances in current and emerging evidence that will help bridge the gap toward faster adoption into patient care.
CME credits: 0.50 Valid until: 25-08-2023 Claim your CME credit at https://reachmd.com/programs/cme/evolving-perspectives-in-pik3ca-related-overgrowth-spectrum-diagnosis-treatment/13790/ PIK3CA-related overgrowth spectrum (PROS) refers to various clinical entities that share the same pathogenetic mechanism. These disorders are caused by somatic gain-of-function PIK3CA mutations. Diagnosis of PROS is often challenging and requires DNA sequencing of the affected tissue. PIK3CA genetic mutations vary greatly depending on the tissue being tested. PROS is not considered an inherited disease. The road to a diagnosis of a rare disease can be a long, winding process. Because of its rarity, a wide spectrum of symptoms, and disease heterogeneity, patients may feel alone and as though they are the only ones with the disease. Management of PROS currently involves symptomatic treatment of its manifestations; an unmet need exists for targeted, systemic therapies. Currently, there is no cure for PROS. This educational activity will assist the interprofessional care team to better understand, apply, and interpret advances in current and emerging evidence that will help bridge the gap toward faster adoption into patient care.
Featuring perspectives from Prof Ghassan Abou-Alfa, including the following topics: Introduction (0:00) Case: A woman in her early 50s with metastatic hepatoid carcinoma of the ovary with an FGFR fusion — Syed M Ahmed, MD, PhD (2:56) Key recent data sets (5:59) Case: A man in his mid 60s with a history of Child-Pugh B cirrhosis and Grade 1 esophageal varices who is receiving atezolizumab/bevacizumab for multifocal HCC — Raji Shameem, MD (22:28) Case: A man in his late 60s with previously treated HCC cirrhosis who is now diagnosed with potentially resectable HCC — Syed F Zafar, MD (29:30) Case: A woman in her late 70s receiving adjuvant anastrozole for Stage I breast cancer who is now receiving atezolizumab/bevacizumab for metastatic HCC — Sunil Gandhi, MD (33:41) Case: A man in his late 70s with metastatic HCC and portal vein thrombosis receiving atezolizumab/bevacizumab (NGS [next-generation sequencing] with PIK3CA mutation, PD-L1 50%) — Susmitha Apuri, MD (35:47) Management of Biliary Tract Cancers (40:18) Case: A man in his late 50s with resected Stage IIB gallbladder cancer s/p adjuvant capecitabine who now has metastatic disease (HER2-positive; MSS, PD-L10) — Nasfat Shehadeh, MD (44:01) Case: A woman in her early 40s with a history of ductal carcinoma in situ and family history of breast cancer, now with metastatic cholangiocarcinoma (NGS with IDH2 mutation) — Joanna Metzner-Sadurski, MD (53:41) CME information and select publications
An interview with Dr. Lynn Henry from the University of Michigan in Ann Arbor, MI, lead author on "Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update." Dr. Henry reviews new biomarkers for the purposes of making treatment decisions for triple-negative breast cancer, and hormone receptor-positive, HER2-negative breast cancer, as well as tumor agnostic tumor biomarkers. Specific biomarkers addressed in this conversation include PIK3CA, ESR1, BRCA 1/2, PALB2, HRD, PD-L1, dMMR/MSI-H, TMB, NTRK, ctDNA, and CTCs. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT 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 asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Lynn Henry from the University of Michigan in Ann Arbor, Michigan, lead author on 'Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update'. Thank you for being here, Dr. Henry. Dr. Lynn Henry: Thank you very much for inviting me to participate. Brittany Harvey: First, 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 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. Henry, do you have any relevant disclosures that are related to this guideline topic? Dr. Lynn Henry: No, I do not. Brittany Harvey: Great! Thank you. Then let's talk about the scope of this guideline. So, what prompted this update to the guideline on the use of biomarkers to guide decisions on systemic therapy for patients with metastatic breast cancer, which was last updated in 2015? And what is the scope of this guideline update? Dr. Lynn Henry: Yes, so a lot has happened in the past six or seven years that influence how we treat metastatic breast cancer. And there are many new drugs that have been approved by the FDA during that time. When we reviewed the prior guideline and the new treatment landscape, we realized that while much of what was included in the old guideline was still relevant, there were quite a number of new biomarkers related to new drugs that needed to be included. The newly recommended biomarkers are primarily applicable to making decisions about treatment of estrogen receptor, progesterone receptor, and HER2-negative breast cancer, also called triple-negative breast cancer, as well as for treatment of hormone receptor-positive HER2-negative breast cancer. And finally, there are now some tumor biomarkers that can be tested for that are tumor agnostic, and these were included as well. Brittany Harvey: Great! So, then let's discuss the updated guideline recommendations based off these new biomarkers for our listeners. The guideline reviews testing for several different biomarkers. So, I would like to review each of the biomarkers that the panel assessed. Let's start with what is the role of PIK3CA mutation testing? Dr. Lynn Henry: Yeah! So, PIK3CA activating mutations are commonly found in tumors that are hormone receptor-positive and HER2-negative. Based on the results of the SOLAR-1 trial, patients whose tumors have an activating PIK3CA mutation had improved progression-free survival when treated with the PI3 kinase inhibitor alpelisib plus fulvestrant compared to fulvestrant alone. This improvement was not seen in patients whose cancers didn't have a mutation. So, therefore, this provided the evidence for the clinical utility of evaluating tumors for the somatic PIK3CA mutations. Testing of either a tumor specimen or plasma to look for PIK3CA mutations can be performed. However, it's important that if the plasma is tested, and no PIK3CA mutations are identified in the circulating tumor DNA, then our tumor specimen should really be tested if possible, because of the possibility of a false negative finding in the plasma. Also, since these mutations can be acquired over time, a more recent specimen should be tested if possible, as opposed to testing the primary tumor. Finally, in the SOLAR-1 trial, a patient's tumor had to have one of the 11 pre-specified PIK3CA mutations in exon 7, 9, or 20. And therefore, when mutations are identified using next-generation sequencing, it is important to confirm that the identified mutation is one of those 11 activating mutations and not a different one that may not convey benefit from treatment with a PI3 kinase inhibitor. Brittany Harvey: Great! I appreciate you're reviewing that recommendation, as well as the clinical utility of it and the evidence behind it. So, then following those recommendations, what is the role of testing for ESR1 mutations? Dr. Lynn Henry: At this time, there are insufficient data to support routine testing of metastatic hormone receptor-positive HER2-negative tumors for ESR1 mutations. However, the panel did note that there's a retrospective analysis of two different phases three trials that demonstrated that fulvestrant improved progression-free survival compared to the aromatase inhibitor exemestane in patients who had previously progressed on a non-steroidal AI and whose tumors had an ESR1 mutation. Importantly, there are ongoing clinical trials addressing this issue, including the PADA-1 trial, which is evaluating the effect of the switch of fulvestrant from aromatase inhibitor therapy, versus remaining on that therapy when ESR1 mutations are detected in the blood. However, although preliminary findings were presented at a recent large breast cancer meeting, and were suggestive of a possible progression-free survival benefit from switching therapy, data have not yet been published, and therefore they were not included in this guideline. Brittany Harvey: Great! So, we'll look forward to those updated data to potentially review that recommendation in the future. So, following those recommendations, what is the role of testing for germline BRCA 1 or 2 and PALB2 pathogenic mutations? Dr. Lynn Henry: So, the answer for germline BRCA1 and BRCA2 mutations is relatively straightforward. Patients with metastatic HER2-negative breast cancer can be either hormone receptor-positive or negative, and who are candidates for treatment with a PARP inhibitor should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine whether they should receive treatment with a PARP inhibitor. This recommendation is based on the results of two large randomized clinical trials comparing PARP inhibitor therapy to physician's choice chemotherapy, although notably, the chemotherapy options did not include taxanes, anthracyclines, or platinums. In contrast, there remains insufficient evidence to support a recommendation either for or against testing for germline PALB2 pathogenic variant for the purpose of determining eligibility for treatment with a PARP inhibitor. The panel did note, however, that there are small single-arm studies that show that there is high response rate to PARP inhibitors in patients with metastatic breast cancer and coding DNA repair defects, such as either germline PALB2 pathogenic variants or somatic BRCA1 or 2 mutations. It was also noted that it is likely that patients who harbored mutations in these genes will actually be identified through routine testing with panel testing for germline variants. Brittany Harvey: Okay, understood. So, then following those recommendations, what is the role of testing tumors for homologous recombination deficiency? Dr. Lynn Henry: So, although there are emerging data from other solid tumors to support the use of homologous recombination deficiency, or HRD testing to guide therapy, current data do not support the assessment of HRD in the management of metastatic breast cancer. Therefore, we did not recommend routine testing of tumors for HRD at this time. Brittany Harvey: It's important to note where we both have evidence and where we don't have evidence. So, then what is the role of testing for expression of PD-L1 in metastatic breast cancer? Dr. Lynn Henry: So, the panel recommends that patients who are candidates for treatment with immunotherapy, with either a PD1 or PD-L1 inhibitor, should undergo testing for expression of PD-L1 in the tumor and immune cells with an FDA-approved test. At present in the United States, pembrolizumab is the only approved immunotherapy for the treatment of metastatic breast cancer, and it is given in combination with chemotherapy. The FDA-approved test for this drug is the 22C3 assay which evaluates PD-L1 staining in the tumor and surrounding stroma to calculate a combined positive score or CPS, with positive considered to be a score of 10 or greater. Of note, in other countries, there are different anti PD1 and PD-L1 antibodies that are approved for treatment, and each has been approved with its own companion diagnostic. So, it is important to make sure that you're using the right biomarker test, depending on which drug you are planning to use. Brittany Harvey: Great! I appreciate you reviewing the test in addition to the role of the biomarker. So, then, following those recommendations, what is the role of testing for deficient mismatch repair microsatellite instability-high? Dr. Lynn Henry: Similar to PD-L1 testing, it is recommended that patients with metastatic breast cancer who are candidates for a treatment regimen that includes an immune checkpoint inhibitor should undergo testing for deficient mismatch repair or microsatellite instability-high to determine eligibility for treatment with one of the drugs that is currently FDA approved, either dostarlimab or pembrolizumab. In contrast to the PD-L1 data, however, there are no randomized studies that have been conducted specifically in patients with breast cancer addressing this question. The testing recommendation was therefore included in these guidelines because of the tumor agnostic FDA approval of these drugs. In terms of which biomarker methodology to use, it was noted that, while the original studies assessed the deficient mismatch repair and MSI high using immunochemistry, and PCR respectively. The FDA has subsequently approved the next-generation sequencing platform to use in selecting candidates for these treatments. And so, therefore, there are a number of different tests that can be used. Brittany Harvey: Thank you for reviewing those recommendations as well. So, then following, what is the role of testing for tumor mutational burden? Dr. Henry Lynn: So, tumor mutational burden describes the quantity of somatic mutations in the tumor. Similar to the biomarkers we were previously discussing, there are minimal data specifically in metastatic breast cancer to support the assessment of tumor mutational burden for making treatment decisions. However, the testing recommendation was again included in the guidelines because of the tumor agnostic FDA approval of the drug pembrolizumab in the setting of high TMB. And also there is one single arm phase two trial that looked at this specifically. Importantly, the panel noted that there are a variety of factors that influence assessment of TMB. These include sample type, pre-analytical factors so how the sample was handled, the size of the panel and mutations that are tested, depths of the sequencing, type of the mutations that are included on the panel, and cut point variables. So, in particular, assessment of TMB in cell-free DNA assays such as circulating tumor DNA is an area of evolving evidence. There are therefore very important caveats to be aware of when selecting a TMB assay and assessing the results, many of which are outlined in the guideline manuscript itself, and different assays can yield different results for the same tissue specimen. It is therefore very important to use the approved companion assay and the approved cut point when making decisions regarding a specific treatment. Brittany Harvey: Absolutely. I appreciate your reviewing those details. So, then what is the role of testing for neurotrophic tyrosine receptor kinase? Dr. Lynn Henry: So, I'm going to abbreviate that to NTRK. So, NTRK fusions are rare in metastatic breast cancer. One study said 0.39% of all breast cancers have NTRK fusions. So, as with the above biomarkers, the NTRK testing recommendation is based on the results of phase 1 and phase 2 studies that were identified by the panel evaluating the efficacy and safety of these inhibitors for the treatment of advanced solid tumors with NTRK gene fusions, noting that there are only minimal data available that are specific to metastatic breast cancer. Brittany Harvey: Understood. Some of these are very rare in metastatic breast cancer. So, then, following that recommendation, what is the role of using circulating tumor DNA? Dr. Lynn Henry: So, for circulating tumor DNA, although the ctDNA technology holds promise in metastatic disease, for its ability to potentially identify tumor-specific mutations that are shed into the blood and that may be targetable, to date, neither the measurement of changes in ctDNA as a marker of treatment responsiveness nor identification of specific mutations in the blood to direct therapy has actually been prospectively shown to improve patient outcomes compared to standard imaging-based detection of tumor progression. Therefore, at present, the guideline does not recommend routine assessment of ctDNA for monitoring response to therapy among patients with metastatic breast cancer, although many studies are underway evaluating this question. Brittany Harvey: Understood. Then the last biomarker that the panel assessed in this guideline update, what is the role of using circulating tumor cells? Dr. Lynn Henry: Similar to circulating tumor DNA, there are insufficient data to recommend routine use of circulating tumor cells to monitor response to therapy among patients with metastatic breast cancer. To date, studies that have examined the clinical utility of this marker to determine the optimal time for treatment change have not led to improvements in outcomes in metastatic breast cancer. Brittany Harvey: Great! Well, thank you for reviewing all of these recommendations. The panel certainly took on a lot of biomarkers and performed a critical review of all the evidence to make recommendations in this setting. So, in your view, Dr. Henry, what is the importance of this guideline update and what should clinicians know as they implement these updated recommendations? Dr. Lynn Henry: Yeah, that's an excellent question. So, this guideline addresses the key questions that we face, as we're making decisions about how best to treat patients with metastatic breast cancer. Importantly, the guideline highlights the current state of the science, with a focus on the available published data from randomized clinical trials. It also discusses the limitations of our current knowledge, as well as key considerations for different biomarkers. Of course, we recognize that there are new data emerging on a regular basis. And the panel therefore also highlighted where data are anticipated but not yet available, as well as key questions which we hope will be able to be addressed in the more distant future. Brittany Harvey: And then finally, how will these guideline recommendations affect patients with metastatic breast cancer? Dr. Lynn Henry: Yeah, so really, that is the bottom line, isn't it? So, ideally, this guideline will enable the dissemination of best practices in terms of biomarker selection and analysis to guide clinicians as they are making treatment decisions in conjunction with patients. Treatment of metastatic breast cancer has become more complex, with regimen selection affected by both inherited germline genetics and somatic changes in the cancer that can evolve over time. The assessment of relevant biomarkers should allow patients to receive the optimal therapies that are most likely to be effective based on the individual characteristics of their cancers. Brittany Harvey: Well, I want to thank you so much for reviewing this guideline with me today, and all of the recommendations and our gaps in evidence, for our listeners. Thank you for your work on this guideline update and thank you for your time today, Dr. Henry. 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 series. 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 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. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you. Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
Listen to a soundcast of the 4/5/2022 FDA approval of Vijoice (alpelisib) for adult and pediatric patients two years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum who require systemic therapy.
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