Podcasts about serds

Dr Rinath Jeselsohn from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

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

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

Dr Rinath M Jeselsohn from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

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.

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

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, New York, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Featuring an interview with Dr Komal Jhaveri, including the following topics: Emerging treatment options for advanced ER-positive breast cancer (0:00) Burstein H. Emerging treatment options for advanced ER+ breast cancer. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01 Discussant. Elacestrant real-world progression-free survival for adult patients with ER-positive, HER2-negative advanced breast cancer: A retrospective analysis using insurance claims in the United States (7:28) Swallow E et al. Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-, advanced breast cancer: A retrospective analysis using insurance claims in the United States. San Antonio Breast Cancer Symposium 2024;Abstract P3-10-08. Ongoing clinical trials involving oral SERDs (9:03) Kaklamani V et al. ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study. San Antonio Breast Cancer Symposium 2024;Abstract P2-08-20. An adjuvant endocrine-based therapy study of camizestrant (AZD9833) in ER+/HER2- early breast cancer (CAMBRIA-2). NCT05952557 Bardia A et al. ELEGANT: Elacestrant versus standard endocrine therapy in women & men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study. San Antonio Breast Cancer Symposium 2024;Abstract P2-08-21. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:48) 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

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, New York, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

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

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

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

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

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  

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

In this episode, I'm thrilled to welcome Dr. Tiffany Troso, a medical oncologist with over 25 years of experience in treating breast and gynecological cancers. We'll unpack some of the most important updates from this year's San Antonio Breast Cancer Symposium (SABCS) in a way that's clear and easy to follow. We'll cover topics like the latest on SERDS and how they're changing treatment options, the practice-changing findings from the PATINA trial, and exciting progress on a TNBC vaccine. Dr. Troso also sheds light on the growing movement toward treatment de-escalation and what it means for creating more personalized approaches to care. This episode is packed with valuable information to help patients and advocates feel informed and prepared to navigate their health journey. A special thank you to our “Your Guide to SABCS sponsors” Lilly, Gilead, Merck, Daiichi-Sankyo and Pfizer for making this episode possible.

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.

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

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/5MJC2024/OralSERDsmBC/2).

Featuring an interview with Dr Seth Wander, including the following topics: ASCO Guidelines Rapid Recommendations Update for Testing for ESR1 Mutations (0:00) Real-world elacestrant use patterns and genomic biomarkers (4:43) Circulating tumor DNA (ctDNA) analyses with imlunestrant in the EMBER Phase I study (8:50) CME information and select publications

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral selective estrogen receptor degraders for ER-positive metastatic breast cancer.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral selective estrogen receptor degraders for ER-positive metastatic breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/5MJC2024/OralSERDsmBC/1).

In this episode, Dr Virginia Kaklamani moderates a discussion with Dr Aditya Bardia and Dr Sarah Sammons answering audience questions on the latest data on the use of oral SERDs therapy, including how to incorporate this new class of therapy into treatment plans for patients with HR+/HER2- breast cancer.Presenters: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, TexasAditya Bardia, MD, MPH, FASCOProfessor of MedicineGeffen School of Medicine at UCLADirector, Breast Oncology ProgramAssistant Chief (Translational Research)Division of Medical OncologyDirector of Translational Research IntegrationUCLA Health Jonsson Comprehensive Cancer CenterLos Angeles, CaliforniaSarah Sammons, MDAssistant Professor of MedicineDana-Farber Cancer Institute Harvard Medical SchoolBoston, Massachusetts Link to full program:https://bit.ly/46hLGcM

In this episode, Manali Bhave, MD; Annalise Labatut, PharmD, BCOP; and nurse practitioner Jamie L. Carroll, CNP, APRN, MSN, begin by discussing the landmark EMERALD study that led to FDA approval of elacestrant, the first oral selective estrogen receptor degrader (SERD) for treatment of hormone receptor–positive/HER2-negative metastatic breast cancer. Dr. Bhave also briefly reviews ongoing clinical trials of other oral SERDs for estrogen receptor–positive/HER2-negative metastatic breast cancer. Next, the panel discusses the possible adverse effects with elacestrant, potential drug–drug interactions, and their personal experiences with managing adverse effects in their patients. Finally, the discussion turns to methods for promoting treatment adherence and persistence and briefly touches on insurance coverage and affordability, including ways that patients and providers can work together to ensure access to approved oral SERDs.Presenters:Manali Bhave, MDPhase I Medical DirectorAssistant ProfessorDepartment of Hematology & Medical OncologyWinship Cancer InstituteEmory UniversityAtlanta, GeorgiaAnnalise Labatut, PharmD, BCOPOncology Clinical Pharmacy Specialist – Breast OncologyEmory Healthcare/Winship Cancer InstituteAtlanta, GeorgiaJamie L. Carroll, CNP, APRN, MSNAssistant Professor of Medical OncologyMayo ClinicRochester, MinnesotaLink to the full program:https://bit.ly/3UT5Be8Claim CME Credit:https://bit.ly/4dBuxhx 

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

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

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York City discusses available and emerging data with oral SERDs for patients with ER-positive metastatic breast cancer. CME information and select publications here (https://www.researchtopractice.com/OncologyTodayOralSERDsmBC23).

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York City discusses available and emerging data with oral SERDs for patients with ER-positive metastatic breast cancer.

Today, we had the pleasure of having Melanie Sisk on the show to demystify the complex world of emerging endocrine therapies, often referred to as the "alphabet soup" of treatments. Melanie provided clarity on the different classes of drugs and how they interact with tumors, particularly focusing on those that target estrogen receptors.We discussed:SERMs (Selective Estrogen Receptor Modulators): These drugs, like tamoxifen, block the growth of cancer cells by competing with estrogen receptors.SERDs (Selective Estrogen Receptor Down Regulators/Degraders): Drugs like Fluvestrant work by degrading estrogen receptors.SERANs (Complete Estrogen Receptor Antagonists): These block both pathways of estrogen, offering a complete blockade.PROTACs: A newer class that targets specific proteins, such as the estrogen receptor, to inhibit cancer growth.+++++++++++++++++++++Attend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramLaura and Will: https://www.instagram.com/laura_and_will/SurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the show

Welcome back to another episode of Breast Cancer Conversations, where we continue to share valuable insights from the San Antonio Breast Cancer Symposium. As a breast cancer survivor and the founder of survivingbreastcancer.org, I'm thrilled to bring you key takeaways from one of the world's largest breast cancer conferences.In this episode, we focus on what to do when CDK4-6 inhibitors, such as Ibrance, Kisqali, and Verzenio, stop working.  Our guest, Amy Bremer, highlights the importance of getting a biopsy to check for mutations, which can be done through a liquid biopsy or a tissue biopsy. This step is crucial for determining the next course of action.We delve into the various treatment options available based on specific mutations. For instance, if your cancer has a PIK3CA mutation, a combination of PIQRAY and Faslodex might be recommended. Other drugs like Trucap, Orserdo, and LSS strontosome are also discussed as potential options for different mutations.For those without mutations, there are still choices available, such as Affinitor plus Faslodex, or considering a switch to a different CDK4-6 inhibitor. We also discuss the possibility of continuing treatment beyond progression or, in cases of aggressive progression, looking into chemotherapy or antibody drug conjugates (ADCs).Stay tuned for our next episode, "on SERDs, SERMs, CERANs, and PROTACs" and remember to subscribe to Breast Cancer Conversations. Please note that our podcast shares personal experiences and is not a substitute for professional medical advice. If you have specific topics in mind or want to be a guest, feel free to reach out to me.Thank you for listening, and let's continue to empower each other through community, education, and resources.00:02:44 - Topic: CDK4-6 Inhibitor Efficacy00:03:31 - Options After Endocrine Therapy and CDK4-6 Inhibitors00:04:35 - Treatment Options Based on Specific Mutations00:05:40 - Options Without Identified Mutations00:06:43 - Inherited Mutations and Treatment Choices00:07:09 - Expert Opinions on Treatment Complexity00:08:44 - Importance of Clinical Trials+++++++++++++++++++++Attend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramLaura and Will: https://www.instagram.com/laura_and_will/SurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the show

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. 

Drs. Hope Rugo and Nancy Davidson discuss the next generation of endocrine therapy in hormone receptor-positive breast cancer – SERDs, SERMs, CERANs, and PROTACs – and challenges relating to the optimal sequence of therapeutic options. TRANSCRIPT Dr. Hope Rugo: Hello, I'm Dr. Hope Rugo, your guest host of the ASCO Daily News Podcast today. I'm a professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco's Comprehensive Cancer Center. Hormone receptor-positive (HR+) breast cancer is the most common subset of this disease and breast cancer is the most common cancer diagnosed in women worldwide. Endocrine therapy (ET) is the cornerstone of management in hormone receptor-positive breast cancer and may involve suppressing estrogen production with aromatase inhibitors in the cancer cell itself, or directly blocking the estrogen receptor pathway through selective estrogen receptor modulators, such as tamoxifen, or the injectable selective estrogen receptor degrader, fulvestrant. However, despite the availability of these therapies, the largest unmet need lies in treatment of HR-positive HER-negative disease lies after progression on endocrine therapy. On today's episode, we'll be discussing the emerging generation of endocrine therapies in breast cancer, some of which were designed to overcome common mechanisms of endocrine resistance, and the challenges relating to the optimal sequence of therapeutic options. Today, I'm delighted to welcome the world-renowned breast cancer researcher, Dr. Nancy Davidson, to the podcast. She's a professor and the executive vice president for clinical affairs at the Fred Hutchinson Cancer Center and professor of medicine at the University of Washington as well as past president of ASCO and AACR. You'll find our full disclosures in the transcript of this episode and disclosures of all guests on the podcast can be found in our transcripts at asco.org/DNpod. Nancy, it's great to have you on the podcast today. Thanks so much for being here. Dr. Nancy Davidson: Thank you so much, Hope, for the opportunity. Dr. Hope Rugo:  You've done incredible work in the area of treating HR+ disease, but also in understanding some of the agents and pathways that are most important to our understanding of how we treat and really think about developing new drugs for HR+ breast cancer. The first generation of anti-estrogen drugs really included selective estrogen receptor modulators, but now we have a new generation of these anti-estrogen drugs. And there's also orally administered selective estrogen receptor degraders, so-called SERDs, that we hope someday will be an alternative with already one approved for the injectable SERD, fulvestrant. But there's a whole additional class of drugs, complete estrogen receptor antagonists, referred to as CERANs, and proteolysis targeting chimerics, PROTACs. These agents are all at various stages of development in both early and metastatic settings and really represent, I think, a confusing array of different treatments that are being studied, some of which of course are approved. Nancy, it would be great if you could tell us some about these exciting new agents, starting with our approved drugs and moving on to the agents that we're studying in clinical trials. Dr. Nancy Davidson: Hope, this is a terrific example of how basic science has really begun to inform clinical practice. For us as breast cancer practitioners, it was really easy for a long time because we only had tamoxifen. And then things like the aromatase inhibitors as a means of decreasing the estrogen ligand came into practice, as did fulvestrant, as you mentioned, a selective estrogen receptor degrader. Thanks though to a lot of understanding about estrogen receptor biology, and specifically, the discovery about a decade ago of estrogen receptor mutations, something that we didn't think exist ed for a long time, but which we now know exists in maybe a third to a half of breast cancers after exposure to aromatase inhibitors, that's led to really an explosion, this alphabet soup of possibilities that you talked about. SERMs, selective estrogen receptor modulators, tamoxifen is the classic one—something that acts as an agonist and as an antagonist, depending on the tissue. The SERDs, the selective estrogen receptor degraders, lead to estrogen receptor destruction. Fulvestrant is the classic example of this right now. But we're very excited that a second one has been FDA approved. That's elacestrant that was approved earlier this year, and it has specifically been developed to try to target those estrogen receptor mutant breast cancers because those are the ones that are particularly resistant. So that's the first of this new generation of SERDs that's coming on the market, has come on the market. As you say, a key advantage there is that it's oral, unlike  fulvestrant, which requires 2 monthly injections and is very, very inconvenient and uncomfortable for patients. Other SERDs are coming along. I think another one that is well along in clinical development is giredestrant, which is in the same family and being tested in clinical trials of the classic varieties. It's been tested in a window trial, looking at its ability to down-regulate Ki67. It's being tested against standard of care in first-line metastatic breast cancer. And there are some studies that are going to begin looking at it in the adjuvant setting as well. There are other members of this particular family, but I think that elacestrant is the one that we have at our fingertips right now, and giredestrant is one that's certainly coming along in clinical trials, and we should look forward to those results. For those who are interested in the giredestrant, the trials in question right now that are going on are persevERA, which is in stage 4 breast cancer, and lidERA, which is in the adjuvant setting. Now that's one new category, or it's an old category with a new twist. A second is these agents that are called complete estrogen receptor antagonists, CERANs, as you talked about them. The key here is that what they do is, the estrogen receptor has a couple of domains, and in particular, it has 2 different activation domains, AFT1 and AFT2. And these CERANs are complete estrogen receptor antagonists, so they block both of those domains. And the hope would be that they might end up being more effective than the other agents that we have available to us right now. So those are also in clinical trial at the present time, and we're waiting to see whether or not there's going be any value in that particular area that's going to able to go forward for us.   Another area that I think we want to talk about is the PROTACs, as you mentioned. These are proteolysis targeting chimeric entities. So, this is a kind of a complicated situation where you have a kind of bivalent situation where you have something that binds both to the estrogen receptor and then also to E3 ubiquinase. So, it leads to degradation again of the agents; that's another area for us to be watching. And then finally the SERCAs. So those are the selective estrogen receptor covalent antagonists, and what they do is they bind very specifically to a cysteine 530 that exists in the estrogen receptor but not in other steroid receptors. So that's where the selective part of this comes along. Now these are all in various stages of clinical investigation. Some of them are pretty early at this point, but I think the ones that are well established are elacestrant, giredestrant is coming along as we just talked about. Camizestrant is also coming along through the SERENA series of trials, and imlunestrant is also coming on through the EMBER series of trials. Hope, I would also be remiss if I didn't go back to an old drug that's a new drug, and that's lasofoxifene, which is also in the SERM family. Those who have been in our field for a while will remember that lasofoxifene was actually originally kind of tested in the prevention setting, where it seemed to have some activity. It came back into our interest because it has really strong activity against estrogen receptor mutant breast cancer models in the laboratory. And as a consequence of that, it's coming back into the clinic through a series of trials that are called the ELAINE trials, where we're looking to see whether or not it might also be better than fulvestrant. It too is an oral agent, so that's a real plus for us, and the first set of ELAINE trials would suggest that there's some nice activity without a lot of toxicity. So, lots going on in this field. You know, I think for all of these things, obviously, we're also working very hard to think about the toxicities. All of these, as I recall, are oral agents. So that gets rid of  1 huge toxicity, which is you don't have the need for some sort of injection. But they all do have some side effects. Frequently, [the toxicities] are like GI side effects or fatigue. In a couple of cases, there might be some concern about cardiac arrhythmias, but I think GI turns out to be one of the most important things that we have seen in some of these trials. Generally, it's very well tolerated, though. I think another important question, which I'm sure is in your head and is in mine, is that how are we going to integrate these into what we already have? And so, I think a lot of the work right now is looking at patients who have already received an aromatase inhibitor plus a CDK4/6 inhibitor and are now going on to one of these new agents. But you might wonder, if they turn out to be effective and well-tolerated, whether they too should be perhaps combined with CDK4/6 inhibitors in place of the aromatase inhibitors or the fulvestrant that we use now. So, I think that we can imagine that those clinical trials are either in progress in some cases or will be coming on as we try to think about how to integrate these new approaches into our existing standard of care, which is already quite complicated, right? We've gone far from tamoxifen, which was good for everybody, to now a really complex algorithm about how we think about hormone therapy, both in early breast cancer and in metastatic breast cancer.  Dr. Hope Rugo: Well, that was a fabulous discussion about the new agents and our existing agents and both the exciting aspects, as well as the challenges. One question that comes up, I think a lot, and this is of course a huge question in many ways, but for ER-positive metastatic breast cancer, where these drugs are first being tested, maybe we'll talk about that first. There's one trial at SERENA-6, looking at camizestrant in patients who have developed evidence of an ESR1 mutation in circulating tumor DNA, who are on first-line therapy with an AI and a CDK4/6 inhibitor. What do you think about that study and where do you think that progress might go? Of course, that's based on data from another trial, which wasn't definitive, but suggested, had sort of a suggestion, you know, without studying the sequencing in detail that maybe you would have improved progression-free survival with that approach. Dr. Nancy Davidson: Yeah, by which you mean the idea of monitoring pre-ESR1 mutations and circulating DNA and then making therapy changes based on that? Is that what you're talking about? Dr. Hope Rugo:  The PADA-1 trial, yes, and that led to this huge SERENA-6 trial, which of course is now accruing. Dr. Nancy Davidson: So, you know, we would love that, right? I think that obviously breast cancer for many years has been interested in trying to have circulating markers that we could use to help to guide our therapy in a more meaningful way than we have in the past. And I think that the trial that you've talked about is certainly one that's trying to make that see whether that's a possibility for us based on information like the PADA trial. I'm hopeful it's going to work out. I would say, let's see what that looks like, whether it's going to be useful or not. It seems to me in some cases, some of these trials have not been quite what we hoped for, but I don't think we necessarily had the molecular techniques or the sensitivity, nor did we necessarily have other things to move to because, you know, those two approaches require both a really good test, but also the ability to use the test to define a new therapy that's going to lead to improved patient outcomes. And I think that these are ingredients that we now have available to us at our fingertips more than we did, say, a decade or 2 decades ago. Exciting approach. Dr. Hope Rugo:  I do think there's a lot of challenges inherent in this process, monitoring blood on a regular basis and following up and then randomizing based on results. But I think [SERENA-6] is an incredibly important trial, as you have mentioned, to try and think about moving past using circulating tumor cells, which didn't work, to just change blindly to the next therapy, but more have a rational reason to change to a drug that may be more effective before the disease itself progresses. And just for our listeners, the unique aspect of trials like this in SERENA-6 is that you change therapy before you have evidence of disease progression, but only this molecular evidence of a mutation that is associated with resistance to the therapy you're on. So, it's a really important question. We'll see what happens, as you mentioned, sometimes we're not clever enough to really get around the fact that there are multiple mutations driving resistance in this setting, so we'll see how straightforward this is. The question also comes up, and I think that's a question with many of these trials now, is they're randomizing patients after a progression on an AI and CDK4/6 inhibitor to receive the novel endocrine therapy or fulvestrant. One of, I think, the concerns of treating oncologists is that then you're sort of eliminating the possibility of a targeted agent in that setting. And of course, we have new targeted agents we're studying as well, AKT inhibitors and new inhibitors of the PI3 kinase pathway. So, the newer trials are now combining, as you mentioned. There's a lot of concerns about drug-drug interactions here and how you might really combine them. And then there are triplet studies looking at CDK4/6 inhibitors, oral SERDs primarily, and pi3-kinase and CDK4/6 inhibitors. What's your thought on these and will they really help to move the needle forward? Dr. Nancy Davidson: I think that's a really interesting question, Hope, is whether or not we're going to find that combination therapies from the get-go are the way to go, or whether we're going to end up having to use maybe more serial therapies. Because not only is it a question about whether or not you can tackle all of these different resistance mechanisms simultaneously, but I think the other question is, as you say, are there negative drug-drug interactions, and are there toxicities that are intolerable? Although these are targeted in all cases and they're relatively benign in terms of side effects from the breast cancer perspective, they're not devoid of toxicity. And so, I think that's going to be another issue for us – whether they're well tolerated during the time that patients are taking them. I guess the other thing I always think about, Hope,  is that it's hard to know about value of cancer care, but you know, we are talking about agents that are not inexpensive. You know, when you think about the financial toxicity, in addition to the side effect toxicity that you and I just talked about, trying to think about what that value is going to look like is going to be very important for us. Also, as somebody who worked for a long time in the lab and in the clinic, you know, there are an infinite number of combinations that you and I could think about that are rational. And so, the question is, how are we going to pick the ones that are the most rational, if you will, the ones that seem to be the most promising, and take them forward into clinical trials? Because patients are our most precious resource. And so, we want to make sure that we are bringing forward only those things that really seem to have a very strong foundation and the opportunity to improve outcomes over time. Tough, tough question for us to try to think about, as you've talked about. The other thing is that, you know, these trials are not only for postmenopausal women, who are the majority of patients, but we also want to target them to premenopausal women. So, in those women, we're also looking at using an LHRH agonist on top of this, right, because many of these things are really at least so far designed for the postmenopausal state. So stay tuned. Lots of work going on. I think one of the interesting things will be making the leap from using these in metastatic disease at time of progression to taking them forward into the early breast cancer space. And several of the agents are now beginning to do that because of very strong preclinical and clinical data to date. Dr. Hope Rugo: So, we have new agents that we're studying in the metastatic setting, and we've seen a trend to move fairly rapidly from phase 1B trials directly into phase 3 trials, because as you pointed out so clearly, there are a number of drugs in this setting, and we don't really know not only which agent is better, but even what class of agents is better. So, as we move more quickly from phase 1B to phase 3, the question comes up about how we're going to study these agents optimally in the early-stage setting. They, I think we all thought that maybe changing based on ctDNA evidence of a mutation might be an approach, but that's complicated. A big question for you is whether or not you think that's ready for prime time as it's being marketed as such. And then the second question is really, are we better changing our whole approach upfront in high-risk disease or should we wait until after patients are exposed to their endocrine therapy and then switch as we go along; the EMBER-4 trial is looking at that switching approach? Dr. Nancy Davidson: Yeah, I think that this is obviously the billion-dollar question for many companies and for many of us as investigators. I don't know that I have a crystal ball into what the best approach might be. We know that already some of these have been abandoned. For example, amcenestrant. So, I don't even have to learn how to say it because it has been abandoned. It did go to phase 3, as you pointed out, in the advanced setting, looking at it with palbo vs letrozole plus palbo, and it didn't really show a whole lot that the company wanted to pursue.  So, I think that sometimes these things are going to be abandoned based on the metastatic setting, which is a large trial, and that's a trial where obviously it might be a little easier to the circulating markers, as you talked about, than maybe in the early-stage breast cancer setting.  I think that probably these early-stage trials are going to end up being big; they're going to have be clean. I'm guessing that most companies and most investigators will want to target them towards high-risk individuals, as you talked about, for 2 reasons. One is that ethically, I think we feel more comfortable with that. These are individuals where standard therapies are maybe not serving them as well as we would like and where we have information to think that we can at least have equipoise about a new approach. And the second is that from a trial design point of view, the event rate is likely to be higher, and therefore you might get answers earlier and with a smaller clinical trial. So that's where I suspect we're going to go. But it's a challenging question, and I think that many investigators and many companies are really trying to struggle with that right now because we do have so many options. And we're not quite sure how to, first, develop these new drugs, but then really importantly, put them in the context of our existing drugs. And as you say, we're also simultaneously trying to develop superior molecular or circulating markers to guide us. So, there's so many variables that are going on right now in this field that, from my point of view, itmakes it really exciting, but it also makes it pretty complicated, both for investigators and for pharma as we try to think about how to position these going forward. But what a great problem to have, Hope, because remember when you and I started in breast cancer, pretty much all you needed to know was tamoxifen. And I think you and I also probably started at the tail end of the time when we were using androgens and progestins and agents that now have basically completely fallen out of favor. Dr. Hope Rugo: Estrogen Dr. Nancy Davidson: Estrogen, yeah, and your side effect profiles were not as good. So, it's a good problem to have. It's a nice situation when science can inform our clinical investigation, our clinical practice. Dr. Hope Rugo: Yes, I think it'll be fascinating to see where we end up at the end, but of course, the complexities of this include the fact that sometimes just the clinical trial design leads to a less than positive result because of the way the trial itself has been designed, which I think is the nice part about moving these earlier into treatment of high-risk disease, but also brings up the question of all sorts of areas we're not really a place to discuss today, like how the statistical design is made, et cetera, that can sometimes result in poor evaluation of excellent agents. One of the questions that comes up, and you brought this up earlier, which I think is really important, is that we are in the era of combining our endocrine agents with targeted agents, and, oral agents, in a fascinating way, really bring up drug-drug interactions in a way that the injectable fulvestrant hasn't, and aromatase inhibitors were kind of quiet on the impacting metabolism, unlike tamoxifen. But we are seeing some drug-drug interactions and certainly the discussions about using these agents may include the question about whether or not you're having more diarrhea or nausea or fatigue or one drug causes photopsia, flashing lights, things like that. Keratitis is becoming a new toxicity to follow.  How are we going to figure out how to sequence these drugs and are they only going to work better all of them as a class in patients with ESR1 mutations in their tumors? Dr. Nancy Davidson: I think we don't know the answer to the second question yet. That's something that really needs to be sorted out. Even if they do, that's still a really important subset of patients, assuming that we continue to start with the aromatase inhibitors, right? That's where those things really seem to emerge right now. I don't know how we're going to figure those things out. I guess that I'm hoping that maybe a couple of agents in these classes will become kind of the lead agents. And so, we'll be able to do this work with a handful of things as opposed to a whole array of things. But we'll see. I think that even within classes, obviously, these agents are going be slightly different, probably. And so it may be that one member of a class may be slightly better from a, maybe not from an efficacy point of view, but from a toxicity point of view. And we'll just have to see how it goes. I don't think I have any magic answers about that. Dr. Hope Rugo: Yes, it'll be interesting to see whether or not the agents work in sequence too. You know, could you use a PROTAC after an oral SERD, for example, or a CERAN? That'll be fascinating to see. Dr. Nancy Davidson:  I'm hoping that preclinical modeling may help with that a little bit, though of course we all know that there are plenty of things that do well in preclinical models, GEMS and rodent models and PDXs, and sometimes those things translate nicely into clinical practice, but sometimes they don't. Dr. Hope Rugo: You mentioned, Nancy, that when we started out, that it was a fairly simple decision about what endocrine therapies, and we ran out very quickly. We're seeing some of those old classes come up with new agents. And you mentioned lasofoxifene, the oral SERM that seems to have some benefits and works in the later-line setting and also can be combined with a CDK4/6 inhibitor; [and also] has data with abemaciclib. There's also a new androgen receptor agonist, enobosarm, that's being tested as well. Do you think that these older mechanisms have a future as well? Dr. Nancy Davidson: I do. I think that because we'll be able to understand the biology better than we did in the past. A lot of our hormone therapy was pretty empiric several decades ago. But I think with better understanding of mechanisms and better understanding of what the patterns of resistance might be for a particular tumor, that we might be able to think about those things. You're right that there's a whole parallel universe right now in androgen receptor targeted therapies that we're not talking about today, both in perhaps in hormone-responsive breast cancers, but also in triple-negative breast cancers in a certain subset. And so that's an area where we probably need to be watching what our prostate cancer colleagues are doing as they develop these agents and thinking about where they might mechanistically make sense to apply in the breast cancer field. It won't be the first time that we've received insights from them because remember, prostate cancer people knew about androgen receptor mutations a really long time before we figured out that they existed in estrogen receptor as well. So, there's a nice cross talk, I think, between the prostate cancer field and the breast cancer field in that regard. Dr. Hope Rugo:  That's an excellent point. And we learn a lot from our colleagues studying other malignancies, and prostate cancer has been a big area there for us and hopefully will help us with studying these agents because there's different toxicity profiles, of course, as well. And then you mentioned the approval of elacestrant, the first oral SERD to have regulatory approval, and it's approved in patients who have ESR1 mutations in their tumors. We're also studying it in the ELEVATE trial in combination with all of the different targeted agents, the CDK4/6 inhibitors, mTOR inhibitor, everolimus, and the PI3 kinase inhibitor, alpelisib, to really try and understand how these can be optimally combined. Would you check for ESR1 mutations at diagnosis of metastatic disease, or would you do this more after progression or start of progression of disease on an aromatase inhibitor? Dr. Nancy Davidson: I tend to be a conservative, Hope, and so unless there's a clinical trial that might be able to be considered, I would tend to check it only after progression on the aromatase inhibitor. But I think some people are earlier adopters, and I suppose it's possible that they might want to know from the get-go. Having said that, I do think elacestrant has an approval after aromatase inhibitor, as I recall. So, presumably the patient would have to have that exposure before you would be able to act on the ESR1 mutation by administering the oral SERD. This is also a new area that may well change with time, right? You know, as we develop different agents, as the agents have different requirements or different indications, and as we perhaps have better tests, it may be things that we don't do routinely now will become very routine in the future. And perhaps in series like you talked about in a serial fashion. Dr. Hope Rugo: Absolutely. I think that's a really important comment about how we're going to think about treating hormone receptor positive disease and potentially, you know, we have new chemo options, of course, not part of our talk discussion today and antibody drug conjugates. So, the future is certainly challenging in terms of understanding this appropriate sequencing. We need data, but it's exciting to have these options. As you pointed out, this is this is a great problem to have, you know, too many drugs with efficacy to try and understand how to use these in the most appropriate way. And as you also pointed out, the use in young women is particularly important. Whether or not you need to suppress the ovaries with all of these new agents is going to be important to understand as well as a next step. I don't know if you have specific thoughts on that area as well. I mean, that may reduce toxicity for younger women. Dr. Nancy Davidson: I guess our approach right now has been to suppress them, but I agree with you; you wonder if you look at some of the mechanisms of action, whether that's really a requirement biologically and medically, or whether it's something that's kind of a leftover from the approval process. You know, that for the drug approval, these women were suppressed. I think we need to work that out because that's another area where certainly women could have ovaries removed. That's pretty straightforward, although it requires a surgical procedure. But otherwise use of LHRH agonists continues to be injections, right? And so, if we're trying to minimize convenience or maximize convenience and minimize toxicity for women with any stage of breast cancer, anything we can do, it seems to me to eliminate an injection is going to be a good thing. So important for us to be able to work that out as well, even though numerically it's a smaller number of women, it's obviously a very important number. population of women. Dr. Hope Rugo: Last question for you. One question that comes up and sent to me and panels all the time is, if you have done your next generation sequencing and you see an ESR1 mutation and a P13CA mutation, what do you prioritize in terms of your choice of treatment, because we have the choice of either using elacestrant or a fulvestrant in combination with an agent targeting the PI3 kinase pathway? Dr. Nancy Davidson: I don't know that there's a right answer to that medically right now. So, when I talk about it with patients, I suggest to them that it's probably not one or the other. It's kind of the question of which one to use first. So, we talk a little bit about side effect profiles. We talk a little bit about patient preference and neither of these drugs is devoid of problems, but sometimes patients have pretty strong feelings about which set of side effects seems the least unattractive to them or the possibility of having those side effects. And I know that if one isn't well tolerated, you can swap over to the other. Dr. Hope Rugo: Absolutely. I think that's a very important way to think about next therapies in our era of not really knowing what's right. And this idea of shared decision-making is so incredibly important. Nancy, thank you so much for sharing your insights and knowledge with us today. I could talk to you for hours about this. Dr. Nancy Davidson: Hope, thank you so much for the opportunity. It is an exciting area and I really enjoyed talking with you about what we know and the many things that we don't yet know, but we're working on. Dr. Hope Rugo: Indeed, it's certainly an exciting time. Thank you to our listeners for joining us today. And thanks to the ASCO Daily News Podcast for highlighting this important area. You'll find a link to all of the studies discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thanks so much.   Disclaimer:    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Follow today's speakers:     Dr. Hope Rugo  @hoperugo  Dr. Nancy Davidson     Follow ASCO on social media:     @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Hope Rugo:  Consulting or Advisory Role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, Eisai, Daiichi Sankyo Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Astellas Pharma, Talho Oncology, Veru, GlaxoSmithKline, Hoffmann-LaRoche AG/Genentech, Inc Travel, Accommodations, Expenses: Merck, AstraZeneca   Dr. Nancy Davidson: No Relationships to Disclose    

La Dra. Eva Ciruelos, Oncóloga Médica del Hospital 12 de Octubre y Vicepresidenta del SOLTI Breast Cancer Research Group, en Madrid, España, nos comenta sobre el cáncer de mama luminal metastásico y el rol del inhibidor de AKT capivasertib y de los inhibidores selectivos del receptor estrogénico (SERDS, por sus siglas en inglés) como amcenestrant, giredestrant, elacestrant y camizestrant.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/YNC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Endocrine therapy, typically with an aromatase inhibitor or fulvestrant plus a CDK4/6 inhibitor, is a mainstay for the management of HR+/HER2- metastatic breast cancer, but many questions still remain about the nuances of optimal use of these and other agents in first- and later-line settings. Furthermore, a number of investigational therapies are showing great promise in HR+/HER2- advanced disease, including novel ER-targeting agents such as oral SERDs, SERMs, SERCAs, PROTACs, and others, as well as antibody–drug conjugates such as those targeting TROP2. It is essential to learn how to best integrate these options into the current treatment arsenal. CDK4/6 inhibition with adjuvant abemaciclib has also changed the standard of care for high-risk patients with earlier-stage disease, but challenges remain, such as determining which patients benefit from this approach, and how to ensure that patients stay on therapy to reduce their risk of recurrence. This PeerView educational activity, based on a recent live symposium and produced in collaboration with GRASP and Living Beyond Breast Cancer to highlight patient perspectives, pairs compelling analyses of key evidence with practically oriented discussions focused on the evolving role of various standard, new, and emerging treatment options for HR+/HER2- advanced and early breast cancer. Leading experts show how to navigate the increasing complexity of treatment in the metastatic setting, as well as the recent expansion of new therapies into early-stage disease, and discuss implications for multidisciplinary care and patient-centric best practices. Upon completion of this activity, participants should be better able to: Describe the rationale for, mechanisms of action of, and latest efficacy and safety data supporting the use of standard, new, and emerging treatment options for patients with HR+/HER2- advanced and early breast cancer, and their evolving roles in clinical practice; Develop personalized treatment plans for patients with HR+/HER2- advanced and early breast cancer that take into account all the relevant tumor-, patient-, and treatment-related factors, and include appropriately selected standard, new, or emerging treatment options in the context of clinical practice or clinical trials; Integrate a team-based, collaborative, and coordinated approach to care to educate patients with HR+/HER2- advanced and early breast cancer about new and emerging treatment options for which they may be eligible and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Host: Jennifer Caudle, DO Guest: Nan Chen, MD Selective estrogen receptor degraders (SERDs) are a novel class of drugs for the treatment of ER+/HER2- advanced breast cancer. So how exactly do they work to treat this type of advanced breast cancer, and what are the findings from recent trials investigating the clinical utility of SERDs? Get the answers to these and other key questions with Dr. Jennifer Caudle and Dr. Nan Chen, Assistant Professor of Medicine at the University of Chicago School of Medicine.

Discussing new SERDs in Hormone Receptor Positive (HR+) from SABCS 2022 - Practice changing studies with Dr. Stephanie Graff, Director of Breast Oncology, Associate Professor of Medicine at Lifespan Cancer Institute, Brown University; Medical Advisor, Dr. Susan Love Foundation CME information and credit available at: https://integrityce.com/courses/clinical-updates-from-san-antonio-her2-advanced-breast-cancer-heavily-pretreated-patients/ Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com  

The $28.7 billion takeout of Horizon Therapeutics by Amgen marks a continuation of the large cap biopharma's return to the inflammatory and autoimmune space where it's been most commercially successful, Associate Editor Stephen Hansen said on the latest BioCentury This Week podcast. Hansen and his BioCentury colleagues discuss the deal's synergies as well as new targets and IL-18 data at the American Society of Hematology (ASH) conference, and the evolving landscape for selective estrogen receptor degraders.

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy

Andreas Hartkopf (Ulm) bespricht in der dritten Folge gleichermaßen gynäkologisch-onkologische Schwerpunkt-Themen sowie hämato-onkologische Highlights. Klar ist für ihn und Harald Müller-Huesmann (Paderborn), dass der Europäische Krebskongress massiv an Bedeutung gewinnt. Denn trotz dessen, dass noch alle an die DESTINY-Breast03-Studie und Standing Ovations in Chicago denken – in Paris werden ebenfalls bedeutsame Ergebnisse präsentiert. Erstmalig wurden Daten zum Gesamtüberleben bei familiär-bedingtem Brust-und Eierstockkrebs vorgestellt: hoch effektiv wirken hier die PARP-Inhibitoren. Und auch für niedergelassene Hämato-Onkolog:innen gab es darüber hinaus eine großartige Session: oral SERDs (=selektive Östrogen-Rezeptor-Down-Regulatoren) sorgen für weiteren Optimismus. -----Diskutieren Sie Montagabend, den 12.09.2022 ab 19:00 Uhr, live mit ausgewiesenen Expert:innen die Highlights des Europäischen Krebskongresses zum Mammakarzinom und den gynäkologischen Tumoren via Zoom! https://go.roche.com/gyn_wrapup

Efficacy data with T-DXd from the DESTINY-Breast04 trial for patients with HER2-low breast cancer; incidence and biologic relevance of HER2 mutations in breast cancer (0:00) Current and potential clinical roles for liquid biopsy in breast cancer; cardiac toxicity with T-DXd in the DESTINY-Breast04 trial (6:10) Safety profile of T-DXd from the DESTINY-Breast04 trial (11:09) Incidence and management of interstitial lung disease caused by T-DXd (14:54) Disease- and patient-specific factors and other considerations in the sequencing of chemotherapy, antibody-drug conjugates, tyrosine kinase inhibitors, SERDs (selective estrogen receptor degraders) and CDK4/6 inhibitors for breast cancer (21:45) Case: A woman in her early 60s with new lobular Stage II breast cancer 20 years after previous breast cancer on the same side (28:39) Case: A woman in her late 20s with a right breast lump and a strong family history of breast cancer (36:12) Case: A woman in her late 30s presenting with right axillary pain who experiences disease progression on T-DM1 and then receives T-DXd (46:09) Future of novel antibody-drug conjugates alone and in combination with immunotherapy for breast cancer (52:35) CME information and select publications

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Go online to PeerView.com/KVE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. CDK4 and 6 inhibitors and endocrine therapy have significantly improved outcomes in ER+/HER2- advanced breast cancer, and recently, the first CDK4 and 6 inhibitor was approved in combination with endocrine therapy in the adjuvant setting for patients with HR+/HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20%. However, pretreated ER+/HER2- breast cancer remains a challenging area with limited treatment options. A number of novel ER-targeting therapies are being investigated in this setting and are showing great promise, including oral selective estrogen receptor degraders (SERDs), selective estrogen receptor modifiers (SERMs), SERD/SERM hybrids, selective estrogen receptor covalent antagonists (SERCAs), and proteolysis-targeting chimeras (PROTACs). This activity, based on a PeerView Live Seminars & Practicum educational web broadcast held in conjunction with the 2022 ASCO Annual Meeting, provides the multidisciplinary breast cancer care team with the latest research and evidence on current and emerging targeted and endocrine therapy options and the implications of these therapeutic advances for practice to ensure that more patients benefit and have improved outcomes. The patient perspective is highlighted as well, and advice for overcoming persistent disparities in breast cancer clinical care are shared. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including CDK4 and 6 inhibitors, SERDs, and SERCAs, and their evolving role in clinical practice; Develop personalized treatment plans for patients with ER+/HER2- breast cancer that take into account recent approvals and safety and efficacy findings from emerging therapies in the context of clinical practice or clinical trials, particularly in areas of high unmet need; and Integrate a team-based, collaborative, and coordinated approach to care, educate patients about new and emerging treatment options for which they may be eligible, and engage patients in shared decision-making to ensure that their unique needs and preferences are taken into account when making treatment decisions.

Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, highlights key advances from the EMBER study and promising data on QOL for HR+/HER2- patients taking checkpoint inhibitors featured at the 2022 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Allison Zibelli, a breast medical oncologist and assistant professor of medicine at the Sidney Kimmel Cancer Center Jefferson Health.  Dr. Zibelli will highlight key posters on breast cancer that will be featured at the 2022 ASCO Annual Meeting. Dr. Zibelli's full disclosures are available in our show notes, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Dr. Zibelli, it's great to have you on the podcast today.  Dr. Allison Zibelli: Thank you. It's nice to be here.  ASCO Daily News: Let's begin with Abstract 1021 and the “Phase 1 EMBER Study.” Can you tell us why this study should be on our radar?  Dr. Allison Zibelli: This study was very interesting because it's testing a novel therapy, which is imlunestrant, an orally bioavailable SERD, or a selective estrogen receptor degrader. This drug is for patients with ER-positive, HER2-negative advanced breast cancer. And they're presenting updated data from the dose-escalation phase and the dose-expansion phase of the EMBER trial.  This trial enrolled 138 patients at a median age of 62 years. The median number of prior therapies for these women was 2. The adverse events were low. They could have prior platinum therapy but no prior fulvestrant or aromatase inhibitor. The premenopausal women in the study received concomitant GnRH antagonist. They had substantial clinical benefit with this therapy with no dose-limiting toxicities.  It had a favorable side effect profile with no cardiac or ophthalmic safety signals, and it had excellent efficacy in patients with heavily pretreated ER-positive advanced breast cancer. This is the first study showing efficacy and safety with an oral SERD. And we're all looking for new oral, well-tolerated therapies for our patients with metastatic estrogen receptor-positive breast cancer.  These patients were heavily pretreated, and they had a median of 2 prior therapies. Most of the patients with advanced breast cancer had prior endocrine therapy, 92% had a prior CDK 4/6 inhibitor, 50% had fulvestrant, and 26% had chemotherapy.  Despite this, they had an overall response rate of 5% with a clinical benefit rate of 47%. So, it'll be very interesting for us to see what happens with this new class of SERDs in the future.  ASCO Daily News: Excellent! So, moving on to Abstract 514. This study addressed patients with high-risk early breast cancer who received pembrolizumab within the new adjuvant biomarker rich I-SPY 2 trial. Can you tell us more about this study?  Dr. Allison Zibelli: This is a very interesting study, which is a platform study comparing various investigational treatments to a standard therapy which was ACT, with or without herceptin, depending on the HER2 status of the patient versus an experimental agent.  One arm of the I-SPY study was neoadjuvant pembrolizumab. This paper is very interesting to me because it's hard to know in advance who will respond to immune checkpoint inhibitors. And that's what this study was designed to answer.  So, they took 69 patients who were on the I-SPY study, they all had high-risk MammaPrint scores, and all of them were HER2 negative, and with these patients, they had 31 complete responses to neoadjuvant pembrolizumab and 38 patients with a residual disease after neoadjuvant pembrolizumab. Notably, of the 31 complete responses, 12 were ER-positive, and 19 were triple-negative.  In the residual disease patients, 28 were ER-positive and 10 were triple-negative. If you compare this with historical data, the response rate for pembrolizumab is about 20% for patients who are triple-negative and about 12% for patients who are ER-positive.  So, the response rates that they had were higher in general. So, what the study did was they found a signature of 53 genes which they named imprint, which was identified with a greater than 90% sensitivity and greater than 80% specificity for predicting complete response to pembrolizumab in all patients.  This worked equally well for the patients who are estrogen receptor-negative and estrogen receptor-positive. In KEYNOTE-086 cohort B, which was presented at the American Association for Cancer Research Annual Meeting (AACR), PD-L1 of greater than 1% only predicted a 23% response rate to pembrolizumab.  So, if we could use the imprint study to predict patients who would respond to pembrolizumab, it would save a lot of needless toxicity and a lot of needless expense, in treating the patients who would have benefit.  So, this is going to be a very useful method to identify patients that we want to treat with pembrolizumab, and perhaps other immune checkpoint inhibitors as well. I think this might be the next “Oncotype” as it were, in that it will be able to predict who will benefit from a specific therapy.  ASCO Daily News: Thank you! Let's move on to Abstract 519. This is a randomized pre-surgical trial of alternative dosing of exemestane in postmenopausal women with early ER-positive breast cancer. What are your key takeaways here?  Dr. Allison Zibelli: I thought this was a great design of a study. It was a window of opportunity for the test. So, what they did was, they tested 3 different dosing schedules of exemestane in patients waiting for surgery for ER-receptor-positive breast cancer.  The patients were randomly assigned to either receive exemestane 20 milligrams a day, the standard schedule, 25 milligrams 3 times a week, or 25 milligrams once a week for 4 to 6 weeks prior to surgery.  Their endpoint was percent decrease in circulating estradiol and what they found was the 3 times a week schedule was comparable to the daily schedule. The once-a-week schedule didn't seem to be adequate to decrease estradiol, but 3 times a week was equivalent to daily.  This was really interesting because we know that our patients have difficulty tolerating aromatase inhibitors. We know from formal studies that about 25% of patients discontinue aromatase inhibitors prematurely because of side effects. Small studies in actual practice settings show it's probably even higher than that—between 30 and 50% of patients discontinue aromatase inhibitors.  So, for the patient that can't tolerate daily therapy, 3 times a week therapy is an attractive option, that may be just as good as daily. I think it is very important for patients who have to take these drugs for years that they have a way to take them that is tolerable.  ASCO Daily News: Absolutely. Well, the last study I'd like to ask you about is Abstract 1015. This looks at the quality of life for patients with HR-positive, HER2 negative advanced breast cancer. So, what does this study tell us about quality of life with different CDK 4/6 inhibitors?  Dr. Allison Zibelli: So, we have a lot of studies of CDK 4/6 inhibitors. And we know that they dramatically improve the overall survival of women with ER-positive metastatic breast cancer. What we also know is that they have a lot of side effects. And for women that have to take these drugs for years, that's important.  So, this study was a matching adjusted indirect comparison study. This is a method that uses individual patient data to create balanced trial populations across separate studies, and they use patients from the MONALEESA-2 trial, which was ribociclib plus AI, compared to MONARCH 3, which used abemaciclib plus AI, the endpoint was something they called “time to sustain deterioration,” which was a decrease in 10 points in the quality of life score, they use the QLQ-C30 questionnaire. The upshot of their data was that ribociclib was more tolerable, mostly with less appetite loss, less diarrhea, and less fatigue than abemaciclib.  So, this is 1 of the first studies we've seen that directly compares, well sort of directly compares the quality of life between these 2 drugs, and this may be a data point that favors ribociclib.  ASCO Daily News: Well, thank you, Dr. Zibelli, for highlighting some really important advances in breast cancer that will be featured at the 2022 ASCO Annual Meeting. We really appreciate it.  Dr. Allison Zibelli: Thank you very much for having me.  ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast. Please take a moment to rate review and subscribe wherever you get your podcasts.  Disclosures:   Dr. Allison Zibelli: None disclosed.  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.     

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Go online to PeerView.com/HCA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in breast cancer discuss the latest advances in the management of patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) breast cancer, including the rapidly accumulating evidence supporting the use of novel therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), selective estrogen receptor covalent antagonists (SERCAs), complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras (PROTACs), among others. In addition to analyzing the recent data from clinical trials with these ER-targeted therapies, patient case scenarios are presented to illustrate their potential role and use, and how to incorporate these novel treatments into the current management paradigm to improve outcomes in patients with ER+ breast cancer. Upon completion of this CE activity, participants will be able to: Cite the rationale for use, mechanism of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Incorporate the most recent efficacy, safety, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations into treatment regimens for eligible patients with HR+ breast cancer in the context of clinical practice or via clinical trial participation.

Dr. Gradishar discusses the evolution of SERDs in breast cancer, novel SERDs that could shift the paradigm of breast cancer treatment, and ongoing research that could solidify the role of these agents in the field.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Go online to PeerView.com/HCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The CDK4 and 6 inhibitors have been game-changers in the management of metastatic HR+, HER2- breast cancer, and accumulating evidence is now showing that they may also provide substantial benefits to some patients in early-stage settings, especially as adjuvant therapy for patients at high risk for disease recurrence. Various novel agents are also emerging as additional options for patients with HR+ breast cancer, including selective estrogen receptor degraders (SERDs) and selective estrogen receptor modulators (SERMs). Rapid developments in the treatment of this subtype of breast cancer provide new hope for further improving outcomes, but they also complicate treatment selection and care decisions for diverse populations of patients with HR+ disease. This PeerView educational activity, based on a recent web broadcast and produced in partnership with the Tigerlily Foundation, focuses on the practicalities of delivering equitable care and individualized treatment to all patients with advanced and early-stage HR+ breast cancer, informed by the latest science, guidelines, and patient needs. Upon completion of this accredited CE activity, participants should be better able to: Cite the rationale for use, mechanisms of action, and features of the various endocrine, targeted, and other therapy options for HR+ breast cancer, Evaluate the most recent efficacy, safety, predictive/prognostic markers, and other key findings from clinical trials assessing different endocrine, targeted, and other emerging therapies and combinations for HR+ breast cancer and the associated relevant practical considerations, Describe the relevant patient-, disease-, and treatment-related factors as well as promising prognostic/predictive markers that could direct selection of endocrine, targeted, and/or other therapies/combinations for patients with HR+ breast cancer, Integrate the latest endocrine, targeted, and/or other treatments/combinations into personalized management plans for eligible patients with HR+ breast cancer in the context of clinical practice or clinical trial participation, according to relevant evidence, best practice recommendations, prognostic/predictive factors, and patient needs and preferences, while addressing disparities in clinical care and research.

Dr. Mayer discusses the mechanism of action of SERDs in ER-positive breast cancer, highlighted data from the AMEERA-1 trial with amcenestrant and palbociclib, and details future research efforts with SERDs.

Erika Hamilton, MD, of the Sarah Cannon Research Institute, and Robert Figlin, MD, of Cedars-Sinai Medical Center, discuss breast cancer research from the 2021 annual meeting of the American Society of Clinical Oncology, including adjuvant and neo-adjuvant breast cancer, metastatic disease, the role of CDK 4/6 inhibitors and PARP inhibitors, the potential of SERDs, and a negative study.