Rounds with the Investigator — A Discussion on the Role of Endocrine-Based Therapy for HR-Positive Breast Cancer — Video Interview

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Consider available clinical trial findings with CDK4/6 inhibitors for localized hormone receptor (HR)-positive, HER2-negative breast cancer, and identify patients for whom adjuvant treatment with one of these agents may be appropriate.
• Evaluate biological and patient- and treatment-related factors to personalize the selection and sequencing of therapy for HR-positive, HER2-negative metastatic breast cancer (mBC).
• Review available research documenting the correlation between the presence of various biomarkers, such as PIK3CA/AKT1/PTEN alterations and ESR1 mutations, and response to specific therapies, and develop optimal molecular testing algorithms for patients with HR-positive mBC.
• Appraise published efficacy and safety data from randomized clinical trials evaluating CDK4/6 inhibitors for HR-positive mBC, and use this information to appropriately counsel patients about the optimal clinical use of these agents.
• Employ evidence-based approaches to targeting PI3K pathway mutations in patients with HR-positive mBC.
• Understand the mechanism of action of, published research findings with and current and future clinical roles for oral selective estrogen receptor degraders for patients with HR-positive mBC.
• Interrogate published Phase III research documenting the efficacy of AKT inhibitors for patients with progressive HR-positive mBC to determine the current clinical applicability of this approach.
• Recognize the side effects and toxicities associated with available and investigational endocrine-based therapies used in the care of patients with breast cancer, and identify management and mitigation strategies.

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HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/SABCS2024/Review/HRPosEndocrine/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Sara A Hurvitz, MD, FACP
Professor
Senior Vice President
Clinical Research Division
Fred Hutchinson Cancer Center
Head, Division of Hematology/Oncology
UW Medicine
Seattle, Washington

Contracted Research: Ambrx, Amgen Inc, Arvinas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Celcuity, CytomX Therapeutics, Daiichi Sankyo Inc, Dantari, Dignitana AB, G1 Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Greenwich LifeSciences Inc, GSK, Lilly, MacroGenics Inc, Novartis, OBI Pharma Inc, Orinove Inc, Orum Therapeutics, Pfizer Inc, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc, Puma Biotechnology Inc, Radius Health Inc, Samumed, Sanofi, Seagen Inc, Stemline Therapeutics Inc, Zymeworks Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: AbbVie Inc, ADC Therapeutics, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Kite, A Gilead Company, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Lilly, Novartis, and Stemline Therapeutics Inc.

Release date: March 2025
Expiration date: March 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Hurvitz

Fasching PA et al. Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial. ESMO 2024;Abstract LBA13.

Goetz MP et al. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: Analyses from the monarchE study. NPJ Breast Cancer 2024;10(1):34. Abstract

Hamilton E et al. Impact of ribociclib dose reduction on efficacy in patients with hormone receptor-positive/human epidermal growth factor receptor-negative (HR+/HER2-) early breast cancer (EBC) in NATALEE. San Antonio Breast Cancer Symposium 2024;Abstract P1-11-16.

Harbeck N et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol 2021;32(12):1571-81. Abstract

Johnston SRD et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol 2023;24(1):77-90. Abstract

Rastogi P et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol 2024;42(9):987-93. Abstract

Rugo HS et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Safety and patient-reported outcomes from the monarchE study. Ann Oncol 2022;33(6):616-27. Abstract

Slamon DJ et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer: Primary results from the phase III NATALEE trial. ASCO 2023;Abstract LBA500.

 

Dr Wander

Finn RS et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. ASCO 2022;Abstract LBA1003.

Goetz M et al. MONARCH 3: Final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy for HR+, HER2- advanced breast cancer. San Antonio Breast Cancer Symposium 2023;Abstract GS01-12.

Hortobagyi GN et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med 2022;386(10):942-50. Abstract

Hortobagyi GN et al. Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). ESMO 2021;Abstract LBA17_PR.

Kalinsky K et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. ASCO 2024;Abstract LBA1001.

Lu Y-S et al. Final results of RIGHT choice: Ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol 2024;42(23):2812-21. Abstract

Slamon DJ et al. Overall survival with palbociclib plus letrozole in advanced breast cancer. J Clin Oncol 2024;42(9):994-1000. Abstract

Sonke GS et al. Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer. Nature 2024;636(8042):474-80. Abstract

 

Dr Goetz

André F et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: Final overall survival results from SOLAR-1. Ann Oncol 2021;32(2):208-17. Abstract

André F et al. Alpelisib for PIK3CA-nutated, hormone receptor-positive advanced breast cancer. N Engl J Med 2019;380(20):1929-40. Abstract

Baselga J et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med 2012;366(6):520-9. Abstract

Chavez-MacGregor M et al. Phase III randomized, placebo-controlled trial of endocrine therapy ± 1 year of everolimus in patients with high-risk, hormone receptor-positive, early-stage breast cancer. J Clin Oncol 2024;42(25):3012-21. Abstract

Goetz MP et al. Landscape of baseline and acquired genomic alterations in circulating tumor DNA with abemaciclib alone or with endocrine therapy in advanced breast cancer. Clin Cancer Res 2024;30(10):2233-44. Abstract

Jhaveri KL et al. Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis. San Antonio Breast Cancer Symposium 2023;Abstract GS03-13.

Juric D et al. First-line inavolisib/placebo + palbociclib + fulvestrant (inavo/pbo+palbo+fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 phase III randomized trial additional analyses. ASCO 2024;Abstract 1003.

Tolaney SM et al. Overall survival and exploratory biomarker analyses of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus chemotherapy in HR+, HER2+ metastatic breast cancer patients. Clin Cancer Res 2024;30(1):39-49. Abstract

 

Dr Jhaveri

Howell S et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: Exploratory analysis of PFS by AKT pathway gene from the phase 3 CAPItello-291 trial. San Antonio Breast Cancer Symposium 2023;Abstract PS17-03.

Howell SJ et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): Overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol 2022;23(7):851-64​. Abstract

Jones RH et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): A multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 2020;21(3):345-57.​ Abstract

Oliveira M et al. Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): Patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2024;25(9):1231-44. Abstract

Oliveira M et al. Capivasertib and fulvestrant for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Subgroup analyses from the Phase 3 CAPItello-291 trial. ESMO Breast 2023;Abstract 187O.

Rugo HS et al. Capivasertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial. ESMO Breast 2024;Abstract 183MO.

Rugo HS et al. Capivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: Characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 study. ESMO Open 2024;9(9). Abstract

Turner NC et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med 2023;388(22):2058-70. Abstract

Turner NC et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the phase III CAPItello-291 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-04.

 

Dr Kaklamani

Bardia A et al. Elacestrant in ER+, HER2- metastatic breast cancer 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

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.

Bidard F-C et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol 2022;40(28):3246-56. Abstract

Chaudhary N et al. CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. NPJ Breast Cancer 2024;10(1):15. Abstract

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;42(35):4173-86. Abstract

Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and combined with abemaciclib, for patients w/ ER+, HER2- advanced breast cancer (ABC), pretreated w/ endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01.

Martin Jimenez M et al. Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study. ESMO 2022;Abstract 211MO.

Martín M et al. Giredestrant for estrogen receptor-positive, HER2-negative, previously treated advanced breast cancer: Results from the randomized, phase II acelERA breast cancer study. J Clin Oncol 2024;42(18):2149-60. Abstract

Oliveira M et al. Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-02.

Rugo H et al. Elacestrant combinations in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase 1b/2, open-label, umbrella study. San Antonio Breast Cancer Symposium 2024;Abstract PS7-06.

Ruiz-Borrego M et al. Results from SERENA-1 parts K/L: A phase 1 study of the next-generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) in combination with ribociclib in women with ER-positive, HER2 negative advanced breast cancer. San Antonio Breast Cancer Symposium 2024;Abstract PS7-08.

Sivakumar S et al. Tissue and liquid biopsy profiling reveal convergent tumor evolution and therapy evasion in breast cancer. Nat Commun 2022;13(1):7495. Abstract

Tolaney SM et al. AMEERA-3: Randomized phase II study of amcenestrant (oral selective estrogen receptor degrader) versus standard endocrine monotherapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol 2023;41(24):4014-24. Abstract

Tolaney SM et al. AMEERA-3, a phase II study of amcenestrant (AMC) versus endocrine treatment of physician’s choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC). ESMO 2022;Abstract 212MO.

Turner NC et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor–positive breast cancer: A combined analysis of the phase III SoFEA and EFECT Ttials. Clin Cancer Res 2020;26(19):5172-7. Abstract