Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 17, Issue 5, Pages 427-436Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2022.2050692
Keywords
Antibody-drug conjugates; gastric cancer; HER2; trastuzumab; trastuzumab deruxtecan
Categories
Ask authors/readers for more resources
Gastric cancer is a common disease worldwide with poor prognosis. Overexpression of HER2 in tumors is associated with poor outcomes. Despite the efficacy of trastuzumab in HER2-positive gastric cancer, subsequent trials of HER2-targeted therapy have been disappointing. However, the antibody-drug conjugate trastuzumab deruxtecan has shown survival benefits in gastric cancer patients who progressed on trastuzumab.
Introduction Gastric cancer is common worldwide, and while multiple therapeutic options exist, the prognosis remains poor. Tumors may overexpress HER2. While targeting HER2 with trastuzumab provides a survival benefit, options following progression are limited. Subsequent trials of HER2-targeted agents failed to improve outcomes. Recently, DESTINY-Gastric01 demonstrated a survival benefit utilizing the antibody-drug conjugate (ADC) trastuzumab deruxtecan in gastric cancer patients that progressed on trastuzumab. Areas Covered /The authors give background to gastric cancer/HER2 and discuss prognostic implications of HER2 overexpression. They also describe initial trials of anti-HER2 therapy, resistance mechanisms, and ADC development/optimization. Finally, the authors review DESTINY-Gastric01 and provide future perspectives. Expert opinion 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available