Talking HER2-Targeted Therapy With Dr. Corcoran

Welcome to a very special series with OncLive! I’m your host today, Caroline Seymour.

OncLive provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

We had the pleasure of speaking with Ryan Corcoran, MD, PhD, associate professor of medicine at Harvard Medical School, gastrointestinal oncologist, director of the Gastrointestinal Cancer Center Program, and scientific director of the Termeer Center for Targeted Therapy at the Massachusetts General Hospital Cancer Center, who discussed key takeaways regarding the use and investigation of HER2-targeted therapies in gastrointestinal malignancies.

The most established role of HER2-targeted therapy is in gastric cancer, wherein approximately 20% of patients will have HER2 overexpression or amplification, said Corcoran. In colorectal cancer, HER2 amplification is less common, found in approximately 4% of patients. Despite this disparity, Corcoran recommends testing these for HER2 with a comprehensive next-generation sequencing panel so that these patients can be directed to appropriate clinical trials, including but not limited to, those with antibody-drug conjugates and bispecific antibodies.

Among these investigational treatment strategies, trastuzumab deruxtecan has demonstrated encouraging phase I data and positive topline findings from the phase II DESTINY-Gastric01 trial. Specifically, topline data with the agent showed improved overall survival versus chemotherapy in patients with heavily pretreated HER2-positive gastric/gastroesophageal cancer. While the data from the phase II trial have yet to be presented, data from the phase I experience showed that the agent led an objective response rate of 43.2% and a disease control rate of 79.5% in patients with advanced gastric/GEJ cancer who had progressed on at least 2 prior regimens, including trastuzumab, 5-FU, and platinum chemotherapy.

Listen on to hear Corcoran discuss the current testing standards and practice patterns surrounding the treatment of HER2-positive gastrointestinal malignancies and provide insight on the current understanding of acquired resistance to HER2-directed therapy.