Dr. Marks on Investigational Antibody-Drug Conjugates in HER2+ Breast Cancer

Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses investigational antibody—drug conjugates (ADCs) in HER2-positive breast cancer.

Ado-trastuzumab emtansine (T-DM1; Kadcyla) is approved for use in patients with HER2-positive breast cancer. The ADC has shown clinical benefit in the early-stage and metastatic settings, says Marks. Several additional ADCs have also shown potential, and are now being evaluated in phase III clinical trials. One such compound is [fam-] trastuzumab deruxtecan (DS-8201), which is being evaluated in the phase III DESTINY trials. Notably, the drug has shown activity in HER2-expressing and HER2-amplified breast cancers. Although patients may experience chemotherapy-related adverse events, such as neutropenia and fatigue, the severity is less than one would expect with traditional cytotoxic chemotherapy, explains Marks.

[Vic-]trastuzumab duocarmazine (SYD985) is a similar compound with a HER2-directed antibody and another payload. The drug also appears promising and is being investigated in the phase III TULIP trials.