Pharmacotherapy for previously treated gastric cancer patients: current options and future developments

Several clinical trials have demonstrated that chemotherapy contributes to prolonged survival in patients with previously treated advanced gastric cancer (AGC).

Currently, cytotoxic agents with established efficacy for previously treated AGC include paclitaxel (PTX), irinotecan (IRI), and trifluridine/tipiracil (FTD/TPI), while the anti-vascular endothelial growth factor(VEGF) agent ramucirumab (RAM) has also shown efficacy. Pembrolizumab is indicated for AGC with microsatellite instability-high (MSI-H) or high tumor mutational burden (TMB). For human epidermal growth factor receptor 2 (HER2)-positive previously treated AGC, trastuzumab deruxtecan (T-DXd) has emerged as the first molecular targeted therapy. Additionally, claudin-18 isoform 2 (CLDN18.2)-targeting antibody therapy has been established as a first-line treatment, with numerous ongoing clinical trials in later-line settings. Other promising molecular targets include trophoblast cell surface antigen 2 (TROP2), cytoplasmic activation/proliferation-associated protein 1(CAPRIN-1), and KRAS. Furthermore, innovative therapeutic approaches such as antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor T-cell (CAR-T) therapy are being developed. This review summarizes the historical and established evidence from clinical trials on previously treated AGC and discusses ongoing clinical trials and future perspectives in treatment development, with a focus on targeted therapies.

Biomarker-driven treatment is expected to become the mainstream approach in the future.