The Right Treatment of the Right Patient: Integrating Genetic Profiling Into Clinical Decision Making in Advanced Gastric Cancer in Asia

Abstract

Gastric cancer is a major global health burden, especially when patients are diagnosed with recurrent or metastatic gastric cancer. Despite recent advances in treatment options with palliative chemotherapy, the median overall survival of patients with gastric cancer remains within 1 or 2 years after the diagnosis of metastatic disease. Gastric cancer is significantly more prevalent in eastern Asia (e.g., Japan and Korea). Next-generation sequencing is rapidly being adopted as part of clinical practice in Korea and Japan, especially in patients with gastric cancer. Approximately 10% to 15% of the patients with gastric cancer who undergo next-generation sequencing of their tumor specimen are allocated to target-matched clinical trials in Japan and Korea. In Japan and Korea, a cell-free DNA next-generation sequencing panel is also actively being investigated as an alternative next-generation sequencing test for patients with gastric cancer, which may reflect the tumor heterogeneity of gastric cancer. In Japan and Korea, multiple biomarkers, such as HER2, mismatch repair, Epstein-Barr virus, PD-L1 (combined positive score), EGFR, FGFR2, and CLDN18.2, are routinely assessed through immunohistochemistry or in situ hybridization before initiation of the first-line treatment in all patients with gastric cancer. Most tertiary cancer centers in Korea routinely perform HER2, mismatch repair, Epstein-Barr virus, and PD-L1 next-generation sequencing before palliative chemotherapy in patients with gastric cancer. Biomarker evaluation for all patients with metastatic gastric cancer enables clinicians to identify available biomarker-based clinical trials early during the course of treatment, which expands treatment opportunities while patients are medically fit for clinical trials, if available. Comprehensive genomic profiling using a tissue or circulating tumor DNA next-generation sequencing panel is considered necessary during second-line or subsequent treatment. It is hoped that a comprehensive molecular profiling strategy will facilitate greater use of precision medicine through molecularly targeted therapies for patients with gastric cancer in the near future.