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Individualizing TROP-2–Directed ADC Therapy in Metastatic Triple-Negative Breast Cancer

Clinical Thought

In this commentary, experts review the evolving role of TROP-2–directed antibody–drug conjugates (ADCs) in metastatic triple-negative breast cancer, with emphasis on first-line treatment selection, sequencing after progression, and management of agent-specific toxicities. The discussion examines phase III data from KEYNOTE-355, ASCENT-04/KEYNOTE-D19, ASCENT-03, TROPION-Breast02, and ASCENT, including progression-free survival, overall survival, response rates, and PFS2, while highlighting important differences in trial design that limit cross-trial comparisons. The experts also address how PD-L1 and germline BRCA1/2 status, prior therapy, disease characteristics, toxicity profiles, supportive care needs, and treatment schedules inform ADC selection and sequencing. Practical considerations related to managing neutropenia, diarrhea, stomatitis, ocular toxicity, and ILD/pneumonitis are reviewed alongside strategies to support timely treatment, toxicity monitoring, biomarker testing, and equitable access to ADC therapy and clinical trials.

Released: September 28, 2026

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Provided by Clinical Care Options, LLC dba Decera Clinical Education.

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Supporters

Supported by an educational grant from Gilead Sciences, Inc.

Gilead Sciences, Inc.

Target Audience

This activity has been designed to meet the educational needs of oncologists and other healthcare professionals involved in the management of patients with triple-negative breast cancer.

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Understand the significance of TROP-2 expression in TNBC and its association with disease progression and prognosis

  • Develop treatment plans incorporating TROP-2–directed ADCs for patients with metastatic TNBC aligned with current evidence, guideline recommendations, biomarkers, prior therapy, and patient-specific factors

  • Evaluate pivotal clinical trial efficacy and safety data for current and emerging TROP-2-directed therapies and combinations in mTNBC

Financial Disclosures

Primary Author

Javier Cortes, MD, PhD: consultant/advisor/speaker: AbbVie, AstraZeneca, Bioasis, Biocon, BioInvent, BioNTech, Bliss, Boehringer Ingelheim, BridgeBio, Circle, Clovis Oncology, Daiichi Sankyo, Delcath Systems, Ellipses, Expres2ion, GEMoab, Gilead, Hexagon, Hibercell, Jazz, Leuko, Lilly, Menarini, Merck Sharp & Dohme, Reveal Genomics, Roche, Scorpion, Seattle Genetics, Zymeworks; honoraria: Astrazeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Stemline, Zuellig; researcher: Ariad, AstraZeneca, Baxalta/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardant, Iqvia, Merck Sharp & Dohme, Pfizer, Piqur, Roche; individual publicly traded stocks and stock options: Leuko; travel/accommodation/expense: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Stemline; royalties or patent beneficiary: Pharmaceutical Combinations of a PI3K Inhibitor and a Microtubule Destabilizing Agent (issued); HER2 as a Predictor of Response to Dual HER2 Blockade (licensed).

Ana C. Garrido-Castro, MD: research (funding to institution): AstraZeneca, Bicycle, BioNTech, Biovica, Bristol Myers Squibb, Case45, Daiichi Sankyo, 4D Path, Foundation, Gilead Sciences, MSD, Novartis, Pfizer, Precede, Reveal Genomics, Stemline, Zenith; consultant/speaker: AstraZeneca, BioNTech, Bristol Myers Squibb, Daiichi Sankyo, Gilead, MSD; other financial or material support: AstraZeneca, Daiichi Sankyo, Gilead, MSD, Pfizer, Stemline.

Additional Disclosures

Generative artificial intelligence (AI) tools were used for data analysis or summarization influencing content. All AI-assisted content underwent human review, editing, and validation by qualified faculty and accredited education staff to ensure scientific accuracy, balance, and compliance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education.