Podcasts about esr1

ADCs as first-line treatment? ESR1 monitoring before progression? Local therapy for CNS disease? Experts tackle today's toughest decisions. Credit available for this activity expires: 11/14/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/charting-course-metastatic-breast-cancer-care-optimizing-2025a1000v4s?ecd=bdc_podcast_libsyn_mscpedu

Featuring an interview with Prof Patrick Neven, including the following topics: Emergence of ESR1 mutations in ER-positive, HER2-negative breast cancer (0:00) Observed toxicity profile of oral selective estrogen receptor degraders (SERDs) (3:57) Emerging data with novel oral SERD combinations (6:31) Challenges for a general medical oncologist in breast cancer (8:41) Sequencing and selection of therapies in ER-positive, HER2-negative breast cancer (12:16) Evaluating the strategy of switching to an oral SERD during first-line endocrine therapy upon "molecular progression" (23:16) CME information and select publications

Is your patient progressing on an aromatase inhibitor (AI)? Fine-tune ddPCR/NGS testing to detect resistance and optimize oral selective estrogen receptor degrader (SERD) success. Credit available for this activity expires: 11/04/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/esr1-mutation-testing-breast-cancer-setting-standard-2025a1000u0f?ecd=bdc_podcast_libsyn_mscpedu

In metastatic breast cancer, resistance to therapy remains one of the most challenging aspects to care. A key driver of resistance in hormone receptor-positive, HER2-negative disease is the ESR1 mutation, a genetic change that alters the estrogen receptor and limits the effectiveness of certain standard therapies. In this episode, CANCER BUZZ speaks with Eleonara Teplinsky, MD, FASCO, head of breast and gynecologic medical oncology at Valley-Mount Sinai Comprehensive Cancer Care, about how the ESR1 mutation shapes treatment decisions and explains communication strategies, such as the "lock-and-key" model. Then CANCER BUZZ speaks with Maimah Karmo, president and CEO of Tigerlily Foundation about the importance of communicating with patients in ways that foster clarity and compassion through relatable analogies. Guest: Eleonora Teplinsky, MD, FASCO Medical Oncologist Valley Mount Sinai Comprehensive Cancer Care Paramus, NJ Maimah Karmo President/CEO Tigerlily Foundation "If you had molecular testing of your tumor done at the time of diagnosis, that may not be enough. If there is disease progression, we might need to repeat it. So it's really important to stress that there are points in the disease course where we're going to be checking for these biomarkers." - Teplinsky "The more that we can know about the tumor, how it's going to behave, what treatment it may or may not respond to, really can help us." - Teplinsky "Having a physician that is a true partner with the patient, that has a relationship, that's trusted, and that feels safe and secure, it's really, really critical." - Karmo Resources: Unlocking the Conversation: Navigating ESR1 Mutations in Metastatic Breast Cancer

As part of the European Society for Medical Oncology (ESMO) Congress 2025, CancerNetwork® spoke with a variety of experts about key takeaways from different late-breaking abstracts, oral presentations, and other sessions focused on potential advancements across cancer care. Presenting investigators highlighted updated results from clinical trials evaluating novel therapeutic strategies across different cancer populations, including breast cancer and lung cancer.  Phase 3 VIKTORIA-1 Trial Sara A. Hurvitz, MD, FACP, the Smith Family Endowed Chair in Women's Health and senior vice president and director of the Clinical Research Division at the Fred Hutch Cancer Center, and tumor chair in breast oncology for the ONCOLOGY® editorial advisory board, first discussed findings from the phase 3 VIKTORIA-1 trial (NCT05501886). Her presentation highlighted how VIKTORIA-1 was “the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival [PFS] with PAM inhibition” for patients with PIK3CA wild-type advanced breast cancer. Data from the trial showed that gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance) produced a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P

Did you know that approximately 50% of breast cancer patients who have been exposed to an aromatase inhibitor (AI) over time in the metastatic setting develop an ESR1 mutation? Credit available for this activity expires: 10/17/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1003008?ecd=bdc_podcast_libsyn_mscpedu

Send us a textIn our Season 11 opening episode, we're bringing you the latest updates from the 2025 ASCO Annual Meeting on metastatic breast cancer. Dr. Ashley Schreier, breast oncologist at Weill Cornell Medicine, breaks down key research and explains what it could mean for people living with MBC.Topics include:Research results for hormone therapy options like camizestrantThe role of ESR1 mutation testingResults from treatment combinations like Enhertu and Perjeta, and Trodelvy and KeytrudaHow to navigate clinical trial accessTips for staying hopeful while exploring treatment optionsWhether you're a patient, caregiver, or advocate, this episode is packed with insights to help you stay informed and empowered.

Featuring case presentations and related discussion from Dr Sara A Hurvitz and Dr Sara M Tolaney, including the following topics: Case: A woman in her mid 50s with localized HR-negative, HER2-positive breast cancer — Dr Tolaney (0:00) Case: A woman in her mid 40s with localized HR-positive breast cancer with a germline BRCA2 mutation — Dr Tolaney (7:08) Case: A woman in her early 30s with HR-negative, HER2-positive metastatic breast cancer with one isolated liver metastasis — Dr Tolaney (11:30) Case: A woman in her early 50s with metastatic triple-negative breast cancer — Dr Tolaney (17:52) Case: A woman in her early 30s with localized HR-positive, HER2-negative breast cancer — Dr Hurvitz (31:49) Case: A woman in her early 60s with HR-positive, HER2-negative metastatic breast cancer with concurrent PIK3CA and ESR1 mutations — Dr Hurvitz (40:39) Case: A woman in her early 40s with recurrent HR-positive advanced breast cancer with a PIK3CA mutation — Dr Hurvitz (51:28) Case: A woman in her early 50s with HR-positive, HER2-negative breast cancer eligible for the SERENA-6 switching strategy — Angela DeMichele, MD, MSCE (58:41) CME information and select publications

Dr. Juan Carlos Samamé, oncólogo médico de Lima, Perú, y vicepresidente de la Latin American Breast Cancer Association (LABCA), da la bienvenida al Dr. Javier Pascual, oncólogo médico del Hospital Universitario Virgen de la Victoria de Málaga, España, y coautor del estudio SERENA-6 (Camizestrant como terapia de primera línea en cáncer de mama luminal avanzado con mutación emergente de ESR1),con quien discutirá los principales resultados:1. ¿En qué consiste el estudio SERENA-6 y cuáles fueron sus objetivos y características principales?2. ¿Porqué, en la primera determinación a los tres o cuatro meses de inicio, cerca de un 55-60% de pacientes tratadas con ciclinas ya presentaba la mutación ESR1?3. ¿Podrían los resultados observados en el SERENA-6 estar relacionados con el tipo de inhibidor de ciclina empleado y cómo se comparan con lo reportado en el estudio PADA-1?4. Sobre la ténica de ctDNA (biopsia líquida): ¿cómo se percibe su acceso en la práctica clínica y cuál es su posicionamiento como biomarcador en este tipo de pacientes para la toma de decisiones terapéuticas?Entre otros. Fecha de grabación: 17 de septiembre de 2025.  Referencia principal:https://www.nejm.org/doi/full/10.1056/NEJMoa2502929Referencia: Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia. Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.

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 

When do you first test for ESR1 mutation in hormone receptor (HR)-positive advanced breast cancer (ABC)? Credit available for this activity expires: 8/7/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002782?ecd=bdc_podcast_libsyn_mscpedu

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, FASCO​Professor of Medicine​Louisa and Rand Glenn Family Chair in Breast Cancer Research​Winship Cancer Institute​Emory UniversityAtlanta, Georgia​Sara M. Tolaney, MD, MPH​Chief, Breast Oncology​Dana-Farber Cancer Institute​Associate Professor of Medicine​Harvard Medical School​Boston, Massachusetts​Content 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

In this episode, CancerNetwork® spoke with breast oncologists Heather McArthur, MD; Erika Hamilton, MD; Hope Rugo, MD; and Paolo Tarantino, MD, PhD, about advances in breast cancer. These developments included recent drug approvals and ongoing research for therapeutic approaches, particularly in the areas of antibody-drug conjugates (ADCs) and CDK4/6 inhibitors, based on presentations they gave at the 25th Annual International Congress on the Future of Breast Cancer (IBC) East in New York City. Initially, McArthur, Komen Distinguished Chair in Clinical Breast Cancer Research at the Harold C. Simmons Comprehensive Cancer Center, discussed immunotherapy use in high-risk triple-negative and HER2-positive disease, the evolving role of adjuvant CDK4/6 inhibition in HER2-negative breast cancer, and potentially transformative advancements in early breast cancer treatment.  She highlighted the FDA approval for pembrolizumab (Keytruda) in early-stage triple-negative breast cancer, promising clinical trials in estrogen receptor (ER)–positive high-risk early-stage breast cancer, and data from an investigator-initiated trial to treat HER2-positive disease. Additionally, she highlighted an 8.5% improvement in pathological complete response with pembrolizumab added to immunotherapy in the phase 3 KEYNOTE-756 trial (NCT03725059), adding that a further event-free survival benefit may complicate the landscape for CDK4/6 inhibition based on lung and liver toxicities associated with the coadministration of these inhibitors with immunotherapy.1 McArthur expressed further excitement for ADC-based combinations for triple-negative disease, as well as in the high-risk residual disease setting. In addition, she highlighted potential advancements in de-escalation strategies and further considerations for ADCs in the HER2-positive and hormone receptor (HR)–positive spaces. Then, Hamilton, director of Breast Cancer and Gynecologic Cancer Research at the Sarah Cannon Research Institute, highlighted emerging therapies for early breast cancer, as well as her use of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) given their recent approvals in various breast cancer subtypes. She also touched upon challenges with respect to the implementation of new therapies for early breast cancer into clinical practice. She initially highlighted new data from the phase 3 VERITAC-2 trial (NCT05654623) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.2 Specifically, findings showed that vepdegestrant, an oral proteolysis-targeting chimera (PROTAC), exhibited an efficacy advantage over fulvestrant (Faslodex) in patients with ESR1-mutant ER-positive, HER2-negative advanced or metastatic disease. Moreover, she highlighted data from the phase 3 DESTINY-Breast09 (NCT04784715) of T-DXd in various combinations for patients with HER2-positive metastatic breast cancer.3 Hamilton further highlighted her implementation of T-DXd into clinical practice, citing her use of the agent in patients with metastatic disease, including those with HER2-low and HER2-ultralow breast cancer. She further differentiated dato-DXd from T-DXd, suggesting that they were different classes of drugs due to their different targets: TROP2 vs HER2. She concluded by highlighting an unmet need regarding sustained benefit from endocrine therapy in HR-positive disease, as well as for ADC sequencing and mechanisms of resistance. Afterward, Rugo, division chief of Breast Medical Oncology, Women's Cancer Program Director, and professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discussed efficacy and safety considerations for CDK4/6 inhibitors in early breast cancer treatment. Specifically, she highlighted their high tolerability despite adverse effects and costs associated with their use. Rugo further touched upon a reduction of recurrence rates associated with CDK4/6 inhibition, although longer-term follow-up data were warranted to optimize the duration of therapy and elucidate survival outcomes. Finally, Tarantino, a research fellow at the Dana-Farber Institute, concluded by discussing sequencing strategies for ADCs, as well as which breast cancer settings or patient populations will experience the greatest impact with this treatment modality. Tarantino discussed his use of the “sandwich strategy,” where he switches the mechanism of action of treatment after using a TOPO1 ADC. Furthermore, Tarantino highlighted data from the DESTINY-Breast09 and phase 3 ASCENT-04 (NCT06100874) trials, which displayed the enhanced efficacy of 2 ADC combination therapies.4 He concluded by discussing future considerations for combining multiple ADCs. References 1. Cardoso F, O'Shaughnessy J, Liu Z, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2- breast cancer: a randomized phase 3 trial. Nat Med. 2025;31(2):442-448. doi:10.1038/s41591-024-03415-7 2. Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. J Clin Oncol. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000 3. Tolaney S, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09. J Clin Oncol. 2025;43(suppl 17):LBA1008. 4. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109

The development of oral selective estrogen receptor degraders (SERDs) represents substantial progress for patients with metastatic breast cancer who have ESR1 mutations. “I'm extremely excited because they're the most effective form of endocrine therapy today,” says Wassim Mchayleh, MD, MBA, the clinical program director of the breast cancer program at AdventHealth Cancer Institute and associate professor of medicine at the University of Central Florida in Orlando. He spoke with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology about SERDs that are currently available and those in development. When it comes to weighing toxicity, “across the board, they are very well-tolerated endocrine therapies with a very low discontinuation rate,” Dr. Mchayleh noted. In addition to recent key clinical trial results, he also looked ahead to what data may help establish the drug class as a replacement for the current standard of care. Dr. Mchayleh reported various financial relationships. Dr. Figlin reported various financial relationships.

In this episode, OncLive On Air® partnered with Two Onc Docs to bring discussion of data from the phase 3 SERENA-6 trial (NCT04964934), which were presented at the 2025 ASCO Annual Meeting. SERENA-6 evaluated switching to camizestrant plus a CDK4/6 inhibitor vs continuing with a standard-of-care aromatase inhibitor plus a CDK4/6 inhibitor in the frontline setting in patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors harbor an emergent ESR1 mutation. Drs Armstrong and Tawagi highlighted key efficacy, safety, and patient-reported outcomes from the study. They also noted the clinical implications of these findings, including how they might be currently applicable to clinical practice, as well as limitations of the research that warrant further investigation. 

This week's episode will be focusing on one of the 2025 plenary sessions: SERENA-6, Camizestrant, a novel selective estrogen receptor degrader (SERD) + CDK 4/6i for tx of emergent ESR1 during 1L endocrine-based therapy + ahead of progression in stage 4 HR+/Her-2 negative breast cancer.We discuss the trial design, endpoints, results, safety concerns, and how it fits into current practice.

Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. 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. More on today's speakers Dr. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

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.

Data from the SERENA-6 trial, presented at the 2025 American Society of Clinical Oncology Annual Meeting, have the potential to dramatically change advanced estrogen receptor–positive, HER2-negative breast cancer care, says William J Gradishar, MD, the Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine in Chicago. The study showed benefit in switching therapies based on circulating tumor DNA evidence of ESR1 mutation, ahead of disease progression. “If we find that the magnitude of benefit seems to be as meaningful as it's been reported to be, then I think what we will find in practice is more and more people will be doing next-generation sequencing testing, doing it earlier, and doing it more frequently to identify these mutations and act upon them,” Dr. Gradishar told Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology. Dr. Gradishar also discussed key drugs in development, including selective estrogen receptor degraders, and questions about the sequencing of new treatments. “There may be diminishing returns, as we've seen with other drugs,” he noted.

In our second plenary episode, we're spotlighting two pivotal phase 3 trials: SERENA-6, which explores ctDNA-guided treatment with camizestrant to delay progression in HR-positive, HER2-negative advanced breast cancer with ESR1 mutations, and NIVOPOSTOP, a landmark study showing improved disease-free survival with adjuvant nivolumab in high-risk, resected head and neck squamous cell carcinoma. Join us as we unpack these practice-changing findings with expert insight and a couple of dad jokes along the way.Studies discussed in the episode:SERENA-6NIVOPOSTOPFor 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.

The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting featured five days of presentations and educational sessions on all types of cancer. Dr. Eleonora Teplinsky, a board-certified medical oncologist at the Valley-Mount Sinai Comprehensive Cancer Center in Paramus, NJ, summarizes the top breast cancer research. Listen to the episode to hear Dr. Teplinsky discuss: The SERENA-6 trial, which found that if metastatic hormone receptor-positive, HER2-negative breast cancer develops ESR1 mutations during first hormonal therapy treatment, switching to camizestrant from an aromatase inhibitor before the cancer grows improves outcomes. Results from the DESTINY-Breast09 trial showing that the combination of Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) and Perjeta (chemical name: pertuzumab) is a better first treatment for metastatic HER2-positive breast cancer than the current standard of THP chemo.  The ASCENT-04/KEYNOTE-D19 trial, which found that people with metastatic, PD-L1-positive, triple-negative breast cancer fared better with the combo of Trodelvy (chemical name: sacituzumab govitecan-hziy) and Keytruda (chemical name: pembrolizumab) as a first treatment compared to people who received chemotherapy and Keytruda.

Dr. John Sweetenham shares highlights from Day 2 of the 2025 ASCO Annual Meeting, including new data on the treatment of ER+/HER2-negative breast cancer and potentially practice-changing results for patients with cutaneous squamous cell carcinoma at high risk of recurrence.  Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, your host of the ASCO Daily News Podcast, welcoming you to our special coverage of the 2025 ASCO Annual Meeting. Today, I'll be bringing you my takeaways on selected abstracts from Day 2 of the Meeting. My disclosures are available in the transcript of this episode.  Today's selection features important, new data on the treatment of ER-positive, HER2-negative breast cancer, the use of tumor treating fields in combination with chemotherapy for locally advanced pancreatic cancer, and potentially practice-changing results for patients with cutaneous squamous cell carcinoma at high-risk of recurrence.  Our first selected abstract is LBA1000. This important phase 3 study was presented by Dr. Erika Hamilton from the Sarah Cannon Research Institute in Nashville and evaluated the use of a novel agent, vepdegestrant, in patients with ER-positive/HER2-negative breast cancer, which had progressed after first-line endocrine therapy. Vepdegestrant is a selective oral PROTAC estrogen receptor degrader, which targets wild-type and mutant estrogen receptor through a novel mechanism of action which directly harnesses the ubiquitin-proteasome system to degrade ER. It has potential advantages over fulvestrant, a selective ER degrader which has to be administered intramuscularly and has limited benefit in patients who progress after endocrine therapy plus a CDK4/6 inhibitor.  Building on the encouraging results from the initial phase 1/2 study of vepdegestrant, Dr. Hamilton reported results from the VERITAC-2 global phase 3 trial, comparing this agent with fulvestrant. The patients in the study had already received treatment with hormone therapy and a CDK inhibitor and were randomly assigned to receive treatment with either vepdegestrant (313 patients) or fulvestrant (311 patients). The vepdegestrant was taken orally each day, while the fulvestrant was given intramuscularly on days 1 and 15 of the first cycle of treatment and day 1 of each subsequent treatment cycle. Patients were stratified by the presence of wild-type ER or ESR1 mutation. A total of 43.3% of patients had ESR1 mutations; 136 of those were in the vepdegestrant group and 134 in the fulvestrant group.   For patients with ESR1 mutations, vepdegestrant significantly increased progression-free survival compared with fulvestrant. For patients who received vepdegestrant, the median PFS was 5 months versus 2.1 months for those who received fulvestrant. The clinical benefit rate was 42.1% in the vepdegestrant group vs. 20.2% in the fulvestrant group. The overall response rate was 18.6% in the vepdegestrant group compared with only 4% in the fulvestrant group.  The PFS and response benefits of vepdegestrant were largely restricted to the population with ESR1 mutations. Overall survival data are currently immature. The safety profile was favorable, with fewer than 5% of patients having dose reductions or discontinuation due to toxicity. The most frequent toxicities were fatigue, nausea, and elevated transaminases.  The authors concluded that oral vepdegestrant demonstrates statistically significant and clinically meaningful improvement in progression-free survival compared with fulvestrant in this group of patients with ESR1-mutated ER+/HER2- advanced breast cancer who have progressed after endocrine therapy and a CDK inhibitor. Patients with recurrent disease in this context are now routinely tested for ESR1 mutations, and this agent is for sure a potential treatment option for them.  The next study on today's episode, LBA4005, reports on the use of tumor treatment fields for patients with locally advanced pancreatic cancer. Tumor treatment fields are electric fields which disrupt cell division and may also induce an enhanced immune response, using a non-invasive portable device attached to the skin, and are already approved for the treatment of some cancers, including GBM and non-small cell lung cancer. A previous phase 2 trial, PANOVA-2, confirmed the feasibility and safety of using this approach in combination with gemcitabine plus or minus nabpaclitaxel in pancreatic cancer. In today's presentation, Dr. Vincent Picozzi from the Virginia Mason Medical Center in Seattle presented the results of the PANOVA-3 trial, a phase 3 study comparing gemcitabine and nabpaclitaxel with the same chemotherapy plus tumor treatment fields in patients with locally advanced pancreatic adenocarcinoma.  Five hundred and seventy-one eligible patients were enrolled in the study with a total of 405 (198 in the treatment field group and 207 in the standard arm) comprising the modified intent- to-treat population. The duration of chemotherapy treatment was comparable in both study arms, and patients receiving treatment fields had a median exposure of almost 27 weeks.  Statistically significant improvements were observed for several study endpoints, including overall survival (a median of 16.2 versus 14.2 months), distant PFS (at 13.9 versus 11.5 months) and pain-free survival (at 15.2 versus 9.1 months), all in favor of the treatment fields arm. Although quality of life data were not reported in detail, the authors noted a significant improvement in global health status in the treatment fields arm. Safety data showed a higher level of skin adverse events in the treatment fields arm but were otherwise as expected for the GnP combination.  These are quite remarkable results which add to the growing evidence base for tumor treatment fields and are particularly compelling in this patient group given the substantial improvement in pain-free survival. It will be especially interesting to see the mature analysis of the quality-of-life endpoints in a subsequent report.  The final selection today is Abstract 6001, which describes the C-POST trial, a phase 3 trial of adjuvant cemiplimab versus placebo in patients with high-risk cutaneous squamous cell carcinoma of the skin. This study was presented by Dr. Danny Rischin from the Peter MacCallum Cancer Centre in Melbourne, Australia.   Although surgical resection with or without adjuvant radiation is curative in 90% of patients with cutaneous squamous cell carcinoma, high-risk features, including nodal disease, skin and subcutaneous metastases, perineural invasion and bone involvement, predict for an inferior prognosis.  Cemiplimab, a PD-1 targeting antibody is standard therapy for patients with locally advanced or metastatic disease who are not candidates for curative surgical resection or radiation therapy, with an overall response rate of almost 50%.  The C-POST study evaluated the use of cemiplimab as adjuvant therapy following surgery and radiation in high-risk patients, compared with placebo. Treatment was administered at 3-week intervals for 12 weeks, and then 6-week intervals for a further 36 weeks, with a primary endpoint of disease-free survival. Four hundred and fifteen patients were randomized in the study, 209 to cemiplimab and 206 to placebo. With median follow-up at 24 months, Dr. Rischin reported a highly significant improvement in disease-free survival for the cemiplimab arm, 49.4 months for placebo versus not reached for cemiplimab, with improvements also observed in the rates of locoregional recurrence and distant recurrence at 80% and 60% reductions, respectively. No new safety signals were observed.  This study is potentially practice-changing and provides strong evidence that cemiplimab should be considered the new standard of care in this clinical context.  Thanks for listening today and join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speaker:   Dr. John Sweetenham   Follow ASCO on social media:    @ASCO on Twitter   @ASCO on Bluesky   ASCO on Facebook   ASCO on LinkedIn    Disclosures:   Dr. John Sweetenham:   No relationships to disclose  

Editor's Note: This interview was recorded shortly before the 2025 American Society of Clinical Oncology Annual Meeting. Big questions associated with ESR1 mutations in patients with hormone receptor–positive breast cancer may soon have answers. New data are “going to take the whole breast oncology field from one place and put it in a different place. It's going to be an inflection point in our history of treating breast cancer,” says Jason Aboudi Mouabbi, MD, assistant professor in the Department of Breast Medical at the University of Texas MD Anderson Cancer Center in Houston. Speaking with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology, Dr. Mouabbi outlined current challenges in identifying and responding to the development of ESR1 mutations. Dr. Figlin and Dr. Mouabbi also discussed how eagerly anticipated findings may transform practice and important aspects of mutational testing to consider. Dr. Mouabbi reported consulting fees from GE Healthcare, Genentech, AstraZeneca, Gilead, Novartis, Fresenius Kabi, BostonGene, and Cardinal Health. Dr. Figlin reported various financial relationships.

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Evaluating first-line treatment of metastatic ER-positive, HER2-positive breast cancer: heredERA Breast Cancer study (0:00) Kuemmel S et al. heredERA Breast Cancer: A phase III, randomized, open-label study evaluating the efficacy and safety of giredestrant plus the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with previously untreated HER2-positive, estrogen receptor-positive locally advanced or metastatic breast cancer. BMC Cancer 2024;24(1):641. Abstract  Treatment outcomes with CDK4/6 inhibitors and with elacestrant in real-world studies (4:13) Lloyd MR et al. CDK4/6 inhibitor efficacy in ESR1-mutant metastatic breast cancer. NEJM Evid 2024;3(5). Abstract  Lloyd M et al. Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC). San Antonio Breast Cancer Symposium 2024;Abstract PS7-05.  Evaluating the CNS activity of imlunestrant, an oral selective estrogen receptor degrader (SERD) (8:06) VandeKopple M et al. Preclinical characterization of imlunestrant, an oral brain-penetrant selective estrogen receptor degrader with activity in a brain metastasis (BM) model. ESMO Breast 2023;Abstract 41P.  Selective review of trials of oral SERDs in the adjuvant setting (11:27) A study of imlunestrant versus standard endocrine therapy in participants with early breast cancer (EMBER-4). NCT05514054 CME information and select publications

Ahead of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with a variety of oncology experts about the late-breaking abstracts, plenary sessions, and other key presentations that may shift the paradigm across different cancer care fields. They highlighted anticipated clinical trial results that may transform the standard of care for gynecologic malignancies, lung cancer, and other disease types. Rachel N. Grisham, MD, section head of Ovarian Cancer and director of Gynecologic Medical Oncology at MSK Westchester of Memorial Sloan Kettering Cancer Center, shared her anticipation of findings from the phase 3 ROSELLA trial (NCT05257408) assessing relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer. She stated she was excited to see if the data may represent a new opportunity for this patient population. Next, MinhTri Nguyen, MD, a medical oncologist and hematologist at Stanford Health Care, highlighted a few breast cancer presentations to look out for. These topics included a plenary session on data from the phase 3 SERENA-6 study (NCT04964934) evaluating camizestrant in combination with CDK4/6 inhibitors for those with hormone receptor–positive, HER2-negative advanced breast cancer harboring emergent ESR1 mutations. Additionally, Eric K. Singhi, MD, assistant professor in the Department of General Oncology in the Division of Cancer Medicine, and assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, spoke about a range of potentially practice-changing results in the lung cancer field. For example, he described a session focused on primary results of the phase 3 IMforte trial (NCT05091567) assessing lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) for those with extensive-stage small cell lung cancer (ES-SCLC). According to Singhi, data from IMforte may shift the paradigm of maintenance therapy for this SCLC population. In the world of head and neck cancer, Douglas R. Adkins, MD, associate professor of Internal Medicine, Division of Oncology, Section of Medical Oncology at Washington University School of Medicine in St. Louis, Missouri, highlighted the session on the phase 3 NIVOPOSTOP GORTEC 2018-01 trial (NCT03576417). Investigators of this study evaluated nivolumab (Opdivo) in combination with chemoradiotherapy for those with resected head and neck squamous cell carcinoma. Adkins noted his excitement to see how these data may impact the standard of care, particularly for patients in Europe, where investigators conducted the study. As part of an Oncology Decoded discussion, Benjamin Garmezy, MD, the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, discussed key abstracts in bladder cancer. One specific presentation included additional findings from the phase 3 NIAGARA trial (NCT03732677), which may show how circulating tumor DNA can influence treatment decision-making regarding perioperative durvalumab (Imfinzi) for patients with muscle-invasive bladder cancer.

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

This featured podcast includes a data review and candid conversation with 4 experts on challenges in the current treatment paradigm for hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC) due to endocrine resistance. This session occurred during a satellite symposium held in conjunction with the 42nd Annual Miami Breast Cancer Conference® in March 2025.  ESR1 mutations are a critical mechanism of resistance, spurring the development of next-generation endocrine agents targeting these mutations. These agents including oral selective estrogen receptor degraders (SERDs) and agents with novel mechanisms, including proteolysis-targeting chimeras (PROTACs), which may offer potential improvements over current treatments. This program will review mechanisms of resistance to current endocrine regimens, strategies to overcome this resistance including comparative mechanisms of novel endocrine agents, emerging data from ongoing clinical trials, and expert perspectives on where these new agents may fit into current algorithms.

Can people diagnosed with metastatic hormone receptor-positive breast cancer avoid chemotherapy and take a CDK4/6 inhibitor instead? Do people diagnosed with DCIS need to have surgery? Will there soon be another oral selective estrogen degrader available? Breastcancer.org medical advisor Dr. Kevin Fox explains the details of the studies and what they mean for you. Listen to the episode to hear Dr. Fox discuss these studies: Young-PEARL: Ibrance plus Aromasin, along with ovarian suppression, offers better progression-free survival than Xeloda for pre-menopausal women with metastatic hormone receptor-positive, HER2-negative breast cancer who had previously received tamoxifen. PATINA: Adding Ibrance to standard-of-care first treatments for metastatic hormone receptor-positive, HER2-positive breast cancer increased progression-free survival by more than a year. EMBER-3:Imlunestrant led to longer progression-free survival than standard therapy if the cancer had an ESR1 mutation among people with estrogen receptor-positive, HER2-negative advanced-stage breast cancer. Adding Verzenio to imlunestrant improved progression-free survival compared to imlunestrant alone, whether the cancer had an ESR1-mutation or not. COMET: Can people with low-risk DCIS just be monitored instead of having surgery with or without radiation? 

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

Featuring an interview with Dr Komal Jhaveri, including the following topics: Imlunestrant, an oral selective estrogen receptor degrader (SERD), with and without abemaciclib for ER-positive, HER2-negative advanced or metastatic breast cancer (0:00) 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. Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2024;[Online ahead of print]. Abstract Rugo HS et al. Elacestrant abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC). San Antonio Breast Cancer Symposium 2024; Abstract PS7-07. Elacestrant for ER-positive, HER2-negative metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the Phase III EMERALD trial by duration of prior endocrine therapy with a CDK4/6 inhibitor and in clinical subgroups (7:40) Bardia A et al. Elacestrant in ER+, HER2- MBC with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract Pharmacokinetics and safety of imlunestrant in patients with hepatic impairment (11:25) Wang XA et al. Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment. San Antonio Breast Cancer Symposium 2024;Abstract P4-10-07. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:15) Lloyd MR et al. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer. Nat Rev Clin Oncol 2024;21(10):743-61. Abstract CME information and select publications

In this episode, Jame Abraham, MD, FACP; William J. Gradishar, MD, FACP, FASCO; and Laura Spring, MD, review key insights and frequently asked questions related to the CDK4/6 inhibitors used to treat patients with early and metastatic hormone receptor (HR)–positive/HER2-negative breast cancer from a live program held in January 2025. Key clinical pearls include:Adjuvant treatment selection recommendations for patients with HR-positive/HER2-negative early breast cancer based on disease and patient characteristics as well as the latest data and guidelines presented by Dr. GradisharTherapeutic strategies for patients diagnosed with HR-positive/HER2-negative metastatic breast cancer (MBC) presented by Dr. AbrahamAddressing challenges related to CDK4/6 inhibitor adherence and adverse event mitigation presented by Dr. SpringPresenters:Jame Abraham, MD, FACPEnterprise Chair and Professor of MedicineDepartment of Hematology and Medical OncologyCleveland ClinicCleveland, OhioWilliam J. Gradishar, MD, FACP, FASCOBetsy Bramsen Professor of Breast OncologyRobert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicago, IllinoisLaura Spring, MDBreast Medical OncologistMass General Hospital Cancer CenterHarvard Medical SchoolBoston, MassachusettsLink to full program including downloadable slides and on-demand webcasts: https://bit.ly/4b5GFqqTo claim credit for listening to this episode, please visit the podcast online at the link above.

Featuring slide presentations and related discussion from Dr Joyce O'Shaughnessy, Dr Mark Pegram and Prof Peter Schmid, including the following topics: Strategies to Identify Patients with HER2-Low and HER2-Ultralow Breast Cancer (0:00) Case: A woman in her mid 50s initially presenting with ER-positive, HER2 IHC 1+ locally advanced breast cancer who experiences progression to HER2 0 metastatic disease (20:53) Case: A woman in her early 60s with ER-positive, HER2 IHC 1+ metastatic breast cancer (mBC) who experiences disease progression 8 months after starting first-line CDK4/6 and aromatase inhibitor (29:14) Expanding the Spectrum of Targeted Therapy (38:52) Case: A woman in her early 60s with HR-positive, HER2 IHC 1+ mBC who receives fifth-line T-DXd resulting in stable disease (1:04:13) Case: A woman in her early 50s with progressive HR-positive, HER2 IHC 0 mBC and an ESR1 mutation who has ultralow HER2 expression on rebiopsy of new liver lesions (1:12:35) Identification and Management of Adverse Events with T-DXd (1:20:27) Case: A woman in her late 40s with HR-positive, HER2 IHC 2+ mBC who experienced persistent low-grade nausea with T-DXd that resolved with olanzapine (1:34:02) Case: A woman in her early 60s with ER-positive, HER2 2+ mBC who received T-DXd resulting in fatigue and asymptomatic interstitial lung disease (1:48:58) CME information and select publications  

Featuring an interview with Dr Seth Wander, including the following topics: Therapy selection after CDK4/6 inhibitor failure: A review of current and investigational treatment for HR-positive, HER2-negative breast cancer Astore S et al. A therapeutic algorithm guiding subsequent therapy selection after CDK4/6 inhibitors' failure: A review of current and investigational treatment for HR+/Her2- breast cancer. Crit Rev Oncol Hematol 2024;204:104535. Abstract (0:00) A preoperative window-of-opportunity study of the oral SERD imlunestrant for newly diagnosed ER-positive, HER2-negative localized breast cancer Neven P et al. A preoperative window-of-opportunity study of oral SERD, imlunestrant, in newly diagnosed ER-positive, HER2-negative early breast cancer: Results from the EMBER-2 Study. Clin Cancer Res 2024;30(23):5304-13. Abstract (3:30) An assessment of an exosome-based ESR1-monitoring RT-qPCR kit that detects acquired resistance variants in liquid biopsy samples Statt S et al. An exosome-based ESR1 monitoring RT-qPCR kit that rapidly and accurately detects acquired resistance variants at ≤ 0.1% frequency in liquid biopsy samples. ESMO 2024;Abstract 420P. (7:08) CME information and select publications

Featuring an interview with Dr Seth Wander, including the following topics: The clinical utility of ESR1 mutations in HR-positive, HER2-negative advanced breast cancer Grinshpun A et al. The clinical utility of ESR1 mutations in hormone receptor-positive, HER2-negative advanced breast cancer. Hematol Oncol Clin North Am 2023;37(1):169-81. Abstract (0:00) Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy for ER-positive, HER2-negative advanced breast cancer Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Phase Ia/Ib EMBER study. J Clin Oncol 2024;[Online ahead of print]. Abstract (6:01) EORTC-2129-BCG: Elacestrant for ER-positive/HER2-negative breast cancer patients with ctDNA relapse Ignatiadis M et al. EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA). ESMO 2024;Abstract 338TiP. (8:20) CME information and select publications  

Welcome back to Oncology for the Inquisitive Mind, where we head back to late 2024 and cover some pivotal trials and ideas from the San Antonio Breast Cancer Conference 2024.This episode broadly covers hormone receptor-positive breast cancer and looks at another CDK comparison (real-world data). While the idea is not new, the potential implications from well-gathered "phase 4" data is a curious discussion point. Other topics include the ESR1 mutation and Imlunestrant, Patritumab Deruxtecan in hormone receptor-positive disease and the role of CTDNA in tumour burden and recurrence in early breast cancerStudies discussed in the episode:SOLTI-VALENTINEEMBER 3ctDNA in EBCCDK ComparisonFor 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 no editorial rights or early previews, and they have access to the episode at the same time you do. Hosted on Acast. See acast.com/privacy for more information.

In this episode, listen to Virginia Kaklamani, MD, DSc; Erica L. Mayer, MD, MPH; and Laura M. Spring, MD, share their clinical insights and takeaways from a live symposium, including from key abstracts presented at the 2024 San Antonio Breast Cancer Symposium:Estrogen Receptor Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerCurrent Guideline Recommendations for When to Pursue ESR1 Mutation Testing Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerChoice and Sequencing of Next Line of Systemic Therapy for ESR1-Mutated Advanced Breast Cancer Based on Tumor Molecular AlterationsOverview of Class-Related and Unique Adverse Events With Approved and Emerging Oral SERDSExpert Recommendations for the Management of Oral SERDs-Related Adverse EventsProgram faculty:Virginia Kaklamani, MD, DScProfessor of MedicineRuth McLean Bowman Bowers Chair in Breast Cancer Research and TreatmentA.B. Alexander Distinguished Chair in Oncology LeaderBreast Oncology ProgramUT Health San AntonioMD Anderson Cancer CenterSan Antonio, TexasErica L. Mayer, MD, MPHDirector of Breast Cancer Clinical ResearchDana-Farber Cancer InstituteAssociate Professor in MedicineHarvard Medical SchoolBoston, MassachusettsLaura M. Spring, MDBreast Medical OncologistMass General Hospital Cancer CenterHarvard Medical SchoolBoston, Massachusetts Resources:To download the slides associated with this podcast discussion, please visit the program page.

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.  

Send us a textIn this episode, we are thrilled to welcome back Tiffany Troso-Sandoval MD, a distinguished medical oncologist with a quarter-century of experience in women's cancers. Dr. Troso shares her insights from a recent breast cancer symposium, illuminating groundbreaking patient care and treatment strategy advancements. As she shares her journey from the clinic to her broader role in cancer advocacy through her company, Winning The Cancer Journey, Dr. Troso unveils some of her plans aimed at educating and empowering both patients and caregivers.We explore the complex world of metastatic breast cancer treatment, emphasizing estrogen receptor-positive cases. We review the different types of anti-estrogen therapies including how and why they work.  We discuss the role of CDK4/6 inhibitors used with aromatase inhibitors, breaking down how these treatments target estrogen pathways to curb cancer growth. We navigate the intricacies of ESR1 mutations and explore how selective estrogen receptor degraders (SERDs) are crucial in overcoming treatment resistance. From chemotherapy timing to empowering caregivers, we delve into the multifaceted nature of breast cancer treatment decisions. Dr. Troso shares her transition from hands-on patient care to creating impactful online resources, highlighting the ongoing nature of the cancer journey for both patients and caregivers.  drtiffanytroso@winningthecancerjourney.comDr. Troso on Facebook Winning The Cancer Journey on FacebookDr. Troso on Instagram Winning The Cancer Journey on TikTok San Antonio Breast Cancer Symposium GuideCNN interview:  https://www.youtube.com/watch?v=MU38D89YlQ0 Are you loving the Test Those Breasts! Podcast? You can show your support by donating to the Test Those Breasts Nonprofit @ https://testthosebreasts.org/donate/ Where to find Jamie:Instagram LinkedIn TikTok Test Those Breasts Facebook Group LinkTree Jamie Vaughn in the News! Thanks for listening! I would appreciate your rating and review where you listen to podcasts!I am not a doctor and not all information in this podcast comes from qualified healthcare providers, therefore may not constitute medical advice. For personalized medical advice, you should reach out to one of the qualified healthcare providers interviewed on this podcast and/or seek medical advice from your own providers .

Featuring an interview with Dr Seth Wander, including the following topics: Design of SERENA-6, a Phase III switching trial of camizestrant for ESR1-mutant breast cancer during first-line treatment Turner N et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 2023;19(8):559-73. Abstract (0:00) EMERALD trial analysis of patient-reported outcomes with oral elacestrant compared to standard of care endocrine therapy for ER-positive, HER2-negative advanced or metastatic breast cancer Cortes J et al. EMERALD trial analysis of patient-reported outcomes (PROs) in patients with ER+/HER2− advanced or metastatic breast cancer (mBC) comparing oral elacestrant vs standard of care (SoC) endocrine therapy. ESMO Breast 2023;Abstract 188O. (5:50) Imlunestrant, an oral selective estrogen receptor degrader, in combination with HER2-directed therapy, with or without abemaciclib, for ER-positive, HER2-positive advanced breast cancer Bhave MA et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study. ASCO 2024;Abstract 1027. (9:43) CME information and select publications

Sagar D. Sardesai, MBBS, discusses the phase 3 ELAINE-3 trial evaluating lasofoxifene plus abemaciclib in ESR1-mutant, ER+/HER2- metastatic breast cancer.

Host: Jennifer Caudle, DO Guest: Virginia Kaklamani, MD Guest: Anne O'Dea, MD When caring for patients with ER-positive/HER2-negative metastatic breast cancer, there's uncertainty on the optimal second-line sequencing of treatments after disease progression on first-line CDK4/6 inhibition and endocrine therapy. But the findings from the EMERALD trial, which led to the approval of ORSERDU® (elacestrant) for patients with ER-positive/HER2-negative ESR1-mutated metastatic breast cancer after disease progression on endocrine therapy,1 contribute to our understanding of second-line treatment options. Dive into the results from the EMERALD trial and subgroup analysis with Drs. Virginia Kaklamani and Anne O'Dea. Dr. Kaklamani is a Professor of Medicine in the Division of Hematology and Medical Oncology at the UT Health Sciences Center in San Antonio, and Dr. O'Dea is a breast medical oncologist at the University of Kansas Cancer Center.

Host: Jennifer Caudle, DO Guest: Virginia Kaklamani, MD Guest: Anne O'Dea, MD When caring for patients with ER-positive/HER2-negative metastatic breast cancer, there's uncertainty on the optimal second-line sequencing of treatments after disease progression on first-line CDK4/6 inhibition and endocrine therapy. But the findings from the EMERALD trial, which led to the approval of ORSERDU® (elacestrant) for patients with ER-positive/HER2-negative ESR1-mutated metastatic breast cancer after disease progression on endocrine therapy,1 contribute to our understanding of second-line treatment options. Dive into the results from the EMERALD trial and subgroup analysis with Drs. Virginia Kaklamani and Anne O'Dea. Dr. Kaklamani is a Professor of Medicine in the Division of Hematology and Medical Oncology at the UT Health Sciences Center in San Antonio, and Dr. O'Dea is a breast medical oncologist at the University of Kansas Cancer Center.

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.      

Featuring a slide presentation and related discussion from Dr Komal Jhaveri, including the following topics: Role of ESR1 mutations in sensitivity and resistance to endocrine therapy in patients with ER-positive metastatic breast cancer (0:00) Efficacy and safety of oral SERDs in patients with ER-positive metastatic breast cancer (13:26) Similarities and differences among available and investigational oral SERDs for ER-positive metastatic breast cancer (24:21) CME information and select publications

Featuring an interview with Dr Komal Jhaveri, including the following topics: Case: A woman in her mid 50s with ER-positive, HER2-low (IHC 1+) metastatic breast cancer with an ESR1 mutation (0:00) Case: A woman in her late 40s with ER-positive, HER2-low ESR1 wild-type metastatic breast cancer who received imlunestrant on a clinical trial (7:25) Case: A woman in her early 60s with a history of localized breast cancer who received imlunestrant and abemaciclib on a trial for newly diagnosed metastatic breast cancer after disease progression on endocrine therapy (12:03) Beyond the Guidelines: A survey of clinical investigator perspectives on the current and future role of oral SERDs (selective estrogen receptor degraders) for ER-positive metastatic breast cancer (17:35) CME information and select publications

New therapeutic options are now available for HR+ MBC.  Dr. Virginia Kaklamani will discuss endocrine therapy resistance, liquid biopsy/blood test, mutations, and treatment sequencing of targeted therapy. You will learn about oral selective estrogen receptor degraders (SERDS), clinical trials, and more.