Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide.¹ Although some chemotherapy (CTx) regimens, including a platinum + fluoropyrimidine combination, trastuzumab [for human epidermal growth factor receptor 2 (HER2)-positive cases], taxanes, irinotecan and ramucirumab, reportedly enhance the survival outcomes of patients with advanced GC (AGC),^2–6 the prognosis remains poor (median survival ~1 year). Although the phase III ATTRACTION-2 trial of anti-programmed death 1 (anti-PD-1) antibody, nivolumab, reported a survival benefit in AGC,⁷ the overall response rate (ORR) was approximately 10% and half of the patients exhibited early disease progression. Thus, the establishment of a better selection of patients who might derive greater benefit from PD-1 blockade is warranted. In addition, trifluridine/tipiracil (TAS-102) demonstrated a survival benefit compared with placebo in heavily pretreated patients with AGC.⁸ However, until recently, several phase III trials of targeting agents for AGC failed to demonstrate a survival benefit (Table 1). Notably, single-agent activity for AGC is minimal, and a few trials have attempted to identify possible biomarkers before phase III trials; thus, better patient stratification based on molecular profiles is crucial.

中文翻译：

---

胃癌的下一代测序和生物标志物：未来是什么？


胃癌（GC）是全球第五大常见癌症，也是全球癌症相关死亡的第三大原因。 ¹据报道，一些化疗 (CTx) 方案，包括铂 + 氟嘧啶组合、曲妥珠单抗 [用于人表皮生长因子受体 2 (HER2) 阳性病例]、紫杉烷类、伊立替康和雷莫芦单抗，可提高晚期 GC 患者的生存结果。 AGC）， ^2-6预后仍然很差（中位生存期约 1 年）。尽管抗程序性死亡 1（抗 PD-1）抗体 nivolumab 的 III 期 ATTRACTION-2 试验报告了 AGC 中的生存获益， ⁷总体缓解率 (ORR) 约为 10%，并且一半患者表现出早期疾病进展。因此，有必要更好地选择可能从 PD-1 阻断中获得更大益处的患者。此外，在接受过多次治疗的 AGC 患者中，曲氟尿苷/替匹拉西 (TAS-102) 与安慰剂相比具有生存获益。 ⁸然而，直到最近，AGC 靶向药物的几项 III 期试验未能证明其具有生存益处（表 1）。值得注意的是，AGC 的单药活性很小，并且一些试验已尝试在 III 期试验之前识别可能的生物标志物；因此，基于分子谱更好的患者分层至关重要。