HER2-Directed ADCs: Updates Across Solid Tumors - Episode 3
Expert Insights on HER2-Directed ADCs in Breast Cancer
Martin Dietrich, MD, PhD, offers a comprehensive review of the efficacy and safety of HER2 ADCs in breast cancer, underscoring their substantial impact on treatment practices in both HER2+ and HER2-low.
Dr. Martin Dietrich and Dr. Ritu Salani discuss the key data on antibody-drug conjugates (ADCs) in the breast cancer space. Dr. Dietrich highlights the role of ADCs in the trastuzumab-refractory HER2-amplified breast cancer setting, with the EMILIA study showing improved responses and tolerability compared to chemotherapy.
The KATHERINE trial demonstrated the efficacy of trastuzumab emtansine (T-DM1) in reducing recurrence rates by 50% in patients who did not achieve pathological complete response after neoadjuvant chemotherapy and surgery. However, the progression-free survival (PFS) was only 9 months, leaving room for improvement.
The DESTINY-Breast01 study introduced trastuzumab deruxtecan (T-DXd), showing a median estimated PFS of over 2 years in the first-line setting. The DESTINY-Breast03 study compared T-DXd against T-DM1 in the second-line setting, demonstrating a four-fold increase in PFS (from 6.8 to 28 months) and establishing a new standard of care for HER2-amplified breast cancer.
The DESTINY-Breast04 study expanded the application of T-DXd to the HER2-low space (IHC 1+ and 2+) in both hormone receptor-positive and negative settings, doubling PFS and showing a 10-month overall survival benefit, particularly in the triple-negative subset. This led to approvals for HER2-low disease, establishing a new second-line standard of care.
Dr. Dietrich emphasizes the importance of biomarker testing, using either FISH plus IHC or IHC in complement with next-generation sequencing. Confirmatory FISH testing is still recommended for equivocal 2+ cases.
Currently, there is no data on using T-DXd after T-DM1 in breast cancer, as the available data focuses on patients refractory to T-DM1 maintenance. An ongoing head-to-head trial is comparing T-DXd against the standard first-line treatment, with the potential to redefine the first-line space in metastatic HER2-amplified breast cancer.
Summary generated by Claude AI.