Application of HER2-Targeted Antibody-Drug Conjugates in the Treatment of Gastric Cancer: A Systematic Review of Pivotal Clinical Evidence
TL;DR
This study systematically portrays the therapeutic level and adverse event spectrum of HER2-ADC, and provides evidence-based support for back-line sequential decision-making and subgroup management.
Abstract
Gastric cancer ranks fifth in the world in the incidence of cancer and the fourth in mortality rate, and HER2 positive accounts for about 15%-20% of advanced gastric cancer. After the HER2 positive first-line regimen was established with trastuzumab combined chemotherapy, there was a long-term lack of standard regimens in the second and posteriary lines. Antibody-drug conjugates (ADCs) realize the accurate delivery of "antibody navigation + chemotherapy warhead" through antibody coupling of high-efficiency cytotoxic loads and dissolving connectors, and produces a bystander effect by releasing the load to penetrate the tumor microenvironment. This study retrieved the 2010-2025 PubMed, Embase and Cochrane databases according to the PRISMA process, and included a total of 15 key phase II/III trials and reviews. The results showed that the median overall survival of trastuzumab deruxtecan (T-DXd) was 3.3 months longer than ramucirumab combined with paclitaxel in the second-line phase DESTINY-Gastric04 (14.7 vs 11.4, HR 0.70), with an objective response rate of 44.3% vs 29.1%; the response rate of DESTINY-Gastric01 in Asia phase II was 51% vs chemotherapy 14%; the response rate of RC48 single-arm phase II in China's original research was 24.4%, with a median overall survival of 7.9 months. Safety is mainly manifested in about 10% of interstitial lung disease and 51% of neutrophil reduction above grade 3. This study systematically portrays the therapeutic level and adverse event spectrum of HER2-ADC, and provides evidence-based support for back-line sequential decision-making and subgroup management.