Cases from the Community: Investigators Discuss the Role of Antibody-Drug Conjugates in the Management of Triple-Negative and HR-Positive Metastatic Breast Cancer — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, breast surgeons, radiation oncologists and other healthcare professionals involved in the diagnosis and treatment of breast cancer.

LEARNING OBJECTIVES

• Review published research data supporting the use of antibody-drug conjugate (ADC) therapy alone and in combination with anti-PD-1/PD-L1 antibodies for patients with newly diagnosed triple-negative metastatic breast cancer (mBC), and use this information to make appropriate treatment recommendations.
• Evaluate published clinical research findings with TROP2-directed ADCs for relapsed/refractory hormone receptor (HR)-positive and triple-negative mBC, and optimally incorporate these agents into the care of eligible patients.
• Assess the biological rationale for the evaluation of HER2-directed ADCs for HER2-low and HER2-ultralow mBC, and identify patients for whom treatment with this approach would be appropriate.
• Discern the side effects and toxicities associated with FDA-approved ADCs employed in the care of patients with mBC, and identify strategies to manage and mitigate these complications.
• Recall ongoing trials evaluating the potential role of novel ADC-based strategies for triple-negative and HR-positive mBC, and as appropriate, counsel patients regarding enrollment.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 1.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. 

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology. 

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology. 

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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/SanAntonioADCsmBC25/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 financial relationships 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:

Javier Cortés, MD, PhD
Head, IBCC International Breast Cancer Center
Barcelona, Spain

Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, AvenCell Europe GmbH, Bioasis Technologies Inc, Biocon, BioInvent, BioNTech SE, Bliss Biopharmaceutical (Hangzhou) Co Ltd, Boehringer Ingelheim Pharmaceuticals Inc, BridgeBio, Circle Pharma, Daiichi Sankyo Inc, Delcath Systems Inc, Ellipses Pharma, ExpreS2ion Biotechnologies, Gilead Sciences Inc, Hexagon Bio, HiberCell, Jazz Pharmaceuticals Inc, Leuko-Labs, Lilly, Menarini Group, MSD, pharmaand GmbH, Reveal Genomics, Roche Laboratories Inc, Scorpion Therapeutics, Seagen Inc, Zymeworks Inc; Contracted Research Funding to Institution: AstraZeneca Pharmaceuticals LP, Baxalta GMBH/Servier Affaires, Bayer HealthCare Pharmaceuticals, Eisai Inc, F Hoffmann-La Roche Ltd, Guardant Health, IQVIA, MSD, Pfizer Inc, PIQUR Therapeutics AG, Roche Laboratories Inc, Takeda Pharmaceuticals USA Inc; Patents: US 2019/0338368 A1, WO 2014/199294 A; Speakers Bureaus:AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, Lilly, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc, Stemline Therapeutics Inc, Zuellig Pharma; Stock OPTIONS — Private Companies: MAJ3 Capital SL; Travel, Accommodation, Expenses: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc, Stemline Therapeutics Inc; Nonrelevant Financial Relationships: Leuko-Labs (stock options, relative), Queen Mary University of London.

Rita Nanda, MD
Director, Breast Oncology
Associate Professor of Medicine
Section of Hematology/Oncology
The University of Chicago
Chicago, Illinois

Advisory Committees: Arvinas, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Exact Sciences Corporation, GE Healthcare, Gilead Sciences Inc, Guardant Health, Lilly, Mabwell Therapeutics Inc, Merck, Moderna, Novartis, Pfizer Inc, Stemline Therapeutics Inc, Summit Therapeutics; Contracted Research: Arvinas, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Corcept Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Relay Therapeutics, Sun Pharma Advanced Research Company, Taiho Oncology Inc.

Professor Peter Schmid, FRCP, MD, PhD
Lead, Centre of Experimental Cancer Medicine
Barts Cancer Institute
London, United Kingdom

Advisory Committees and Consulting Agreements: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals Inc, Celgene Corporation, Eisai Inc, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, Roche Laboratories Inc; Contracted Research: Astellas, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Medivation Inc, a Pfizer Company, Merck, Novartis, OncoGenex Pharmaceuticals Inc, Roche Laboratories Inc.

Priyanka Sharma, MD
Frank B Tyler Professor in Cancer Research
Division of Medical Oncology, Department of Internal Medicine
Co-Program Leader
Drug Discovery, Delivery and Experimental Therapeutics Program
The University of Kansas Cancer Center
Westwood, Kansas

Advisory Committees: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Gilead Sciences Inc, Menarini Group, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc; Contracted Research: Bristol Myers Squibb, Gilead Sciences Inc, Novartis; Data and Safety Monitoring Boards/Committees: Jazz Pharmaceuticals Inc.

MODERATOR — 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: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, 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, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, 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, Nuvation Bio Inc, 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, Sumitomo Pharma America, 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 financial relationships 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 Gilead Sciences Inc and Helsinn Therapeutics (US) Inc.

Release date: January 2026
Expiration date: January 2027

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

Prof Schmid

Cortés J et al. Primary results from ASCENT-03: A randomized phase 3 study of sacituzumab govitecan vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer who are not candidates for PD-(L)1 inhibitors. ESMO 2025;Abstract LBA20.

Cortés J et al. Sacituzumab govitecan in untreated, advanced triple-negative breast cancer. N Engl J Med 2025;393(19):1912-25. Abstract

Dent R et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial. ESMO 2025;Abstract LBA21.

Punie K et al. Patient-reported outcomes (PROs) with Sacituzumab govitecan (SG) vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors in the phase 3 ASCENT-03 study. San Antonio Breast Cancer Symposium 2025;Abstract RF6-05.

Schmid P et al. A single-arm phase 2 study of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer (mBC) (ASPEN-09-03).ESMO 2025;Abstract 623TiP.

Tolaney SM et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. ASCO 2025;Abstract LBA1008.

Dr Sharma

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. J Clin Oncol 2024;391(22):2110-22. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;Abstract LBA1000.

Fan Y et al. Sacituzumab tirumotecan (sac-TMT) vs investigator’s choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): Results from the randomized, multi-center phase III OptiTROP-Breast02 study. ESMO 2025;Abstract LBA23.

Jhaveri KL et al. Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07. San Antonio Breast Cancer Symposium 2025;Abstract GS1-09.

Modi S et al. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: Long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med 2025;31(12):4205-13. Abstract

Pristilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial. ESMO Virtual Plenary 2025;Abstract VP1-2025.

Dr Nanda

Bardia A et al. Final results from the randomized phase III ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol 2024;42(15):1738-44. Abstract

Colombo R et al. The journey of antibody-drug conjugates: Lessons learned from 40 years of development. Cancer Discov 2024;14(11):2089-108. Abstract

Huppert LA et al. Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC). NPJ Breast Cancer 2025;11(1):34. Abstract

Mai N et al. Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan. ASCO 2024;Abstract 1085.

Modi S et al. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: Long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med 2025;31(12):4205-13. Abstract

Pan Y et al. Exploring intra-tumor heterogeneity in malignant peripheral nerve sheath tumors through single-cell multi-omics. AACR 2024;Abstract 3888.

Poumeaud F et al. Efficacy of administration sequence: Sacituzumab govitecan and trastuzumab deruxtecan in HER2-low metastatic breast cancer. Br J Cancer 2024;131(4):702-8. Abstract

Tarantino P et al. Outcomes of subsequent treatment regimens after trastuzumab deruxtecan in patients with metastatic breast cancer. J Natl Cancer Inst 2025;117(11):2327-35. Abstract

Yin Y et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: A randomized phase 3 trial. Nat Med 2025;31(6):1969-75. Abstract

Dr Cortés

Park YH et al. Nausea and vomiting in an evolving anticancer treatment landscape: Long-delayed and emetogenic antibody-drug conjugates. Future Oncol 2025;21(10):1261-72. Abstract

Pérez-García JM et al. Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): An open-label, single-arm, phase 2 trial. EClinicalMedicine 2025;85:103309. Abstract

Rugo H et al. US expert Delphi consensus on the prevention and management of stomatitis in patients treated with datopotamab deruxtecan. Support Care Cancer 2025;33(9):756. Abstract

Schmid P et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study. ESMO Breast Cancer Annual Congress. 2024;Abstract LBA4.

Tarantino P et al. Real-world efficacy of immediate subsequent lines of therapy after trastuzumab deruxtecan (T-DXd) in patients with metastatic breast cancer (MBC) – retrospective study from the nationwide Flatiron database. San Antonio Breast Cancer Symposium 2024;Abstract P1-08-08.