Year in Review: HER2 and TROP2 Antibody-Drug Conjugates in Breast Cancer
Dr. Irene Kang from City of Hope Orange County and Dr. Megan Kruse from Cleveland Clinic reviewed transformative advances in HER2- and TROP2-directed antibody drug conjugates (ADCs) across breast cancer subtypes. The discussion emphasized 2025 and 2026 as a boom period with ADCs expanding from later-line HER2-positive therapy to cornerstone treatments across hormone receptor-positive, triple-negative, and early-stage disease settings. Key clinical updates included DESTINY-Breast09 challenging the CLEOPATRA standard in first-line HER2-positive metastatic disease, brain metastases management advances through DESTINY-Breast12, and early-stage integration via DESTINYBreast-05 and -11. TROP2-targeted therapy selection focused on toxicity differentiation between sacituzumab govitecan and datopotamab deruxtecan, with practical scheduling and side effect management considerations driving decisions. Triple-negative breast cancer advances featured ASCENT-04 establishing sacituzumab govitecan plus pembrolizumab as first-line standard for PD-L1-positive disease, whereas ASCENT-03 and TROPION-Breast02 provided options for PD-L1-negative patients. Future priorities include developing alternative payload ADCs, investigating combination strategies, and understanding resistance mechanisms through ongoing translational research and real-world sequencing studies to optimize treatment paradigms.
Year in Review: HER2 and TROP2 Antibody-Drug Conjugates in Breast Cancer
Dr. Irene Kang from City of Hope Orange County and Dr. Megan Kruse from Cleveland Clinic introduce this OncLive Insights program reviewing HER2 and TROP2-directed antibody drug conjugates (ADCs) in breast cancer. Dr. Kruse emphasizes that 2025 and 2026 represent a transformative period for ADCs, with expanding utility across all breast cancer subtypes and treatment settings. Previously confined to later-line therapy or HER2-positive disease, ADCs now have indications spanning hormone receptor-positive, HER2-positive, and triple-negative breast cancer (TNBC) across first-line, second-line, and later-line settings, with increasing penetration into early-stage disease.
Dr. Kruse addresses patient selection for TROP2-targeted ADC therapy, noting that TROP2 expression intensity does not correlate with therapeutic efficacy. The current therapeutic landscape includes datopotamab deruxtecan (Dato-DXd) and SG, each with distinct toxicity profiles. Selection decisions involve multifactorial considerations including disease progression patterns, prior progression-free survival (PFS) duration, disease location (visceral versus bone-only), and individual patient preferences regarding treatment scheduling and toxicity management.
Dr. Kruse discusses DESTINY-Breast09 as a transformative study challenging the long-standing CLEOPATRA regimen (docetaxel, trastuzumab, pertuzumab) for first-line HER2-positive metastatic breast cancer.
Dr. Kruse addresses the complexity introduced by simultaneous release of DESTINY-Breast05 and -11 data, requiring contextualization of both neoadjuvant and adjuvant approaches.
Dr. Kruse reviews ASCENT-03 and TROPION-Breast02 data for PD-L1-negative or checkpoint inhibitor-ineligible metastatic TNBC, noting unsurprising ADC superiority in first-line treatment.
