An overview of the preclinical discovery and development of trastuzumab deruxtecan: a novel gastric cancer therapeutic

While the 2010 ToGA trial demonstrated efficacy of trastuzumab in HER2 positive gastric cancer, subsequent trials of HER2-directed therapy have disappointed. Downregulation of HER2 after trastuzumab may play a role; however, trastuzumab deruxtecan maintains some efficacy in low-level HER2 expressing tumors. The DESTINY-Gastric01 cohort was from South Korea/Japan; authors have reported differences in gastric cancer risk factors/physiology between Eastern and Western populations. DESTINY-Gastric02 will evaluate trastuzumab deruxtecan in Western patients to confirm generalizability. Pulmonary side effects are notable;physicians must be cognizant of overlapping toxicities with combination therapy.