晚期胃癌免疫检查点抑制剂治疗的临床研究进展

Progression in immunotherapy with immune checkpoint inhibitors for advanced gastric cancer

晚期胃癌治疗方法有限,预后较差。2017年,针对程序性死亡蛋白-1(programmed cell death protein-1, PD-1)和程序性死亡配体-1(programmed death ligand-1, PD-L1)的免疫检查点抑制剂获批用于晚期胃癌治疗,提示胃癌免疫治疗时代已经到来。然而,相对于肺癌,免疫检查点抑制剂尚未获批用于胃癌一、二线治疗。目前,大量胃癌免疫治疗临床试验正在进行中,其模式还在进一步优化,包括免疫联合化疗、免疫检查点抑制剂联合其他免疫治疗及新型免疫检查点抑制剂的应用等,同时寻找合适的肿瘤标志物,筛选优势人群用于胃癌精准免疫治疗。本文着重讨论晚期胃癌免疫检查点抑制剂治疗的临床研究最新进展。

Advanced gastric cancer is one of cancer types with poor prognosis in East Asia and China.Treatment strategies are espe- cially limited in patients with advanced gastric cancer due to the lack of potent eftqcacy and serious toxicity.In 2017,immune checkpoint inhibitors targeting programmed cell death protein-1(PD-1)or programmed death ligand-1(PD-L1)have been approved by FDA for treating advanced gastric or gastroesophageal junction cancer (GC/GEJC)as a third-line option.However,immune checkpoint inhibitors have not been used in the first or second-line setting for advanced gastric cancer.Presently,many clinical trials are undergoing to determine the efficacy of combined therapy including checkpoint inhibitor plus chemotherapy,dual combinations with two immune checkpoint inhibitors,to enhance anticancer activity of immune checkpoint inhibitors and expand targeted patients.Furthermore,areas for further study include the development and validation of novel biomarkers to predict patients who are most likely to respond to treatment and characterization of outcomes with immune checkpoint inhibitors in different defined disease subgroups.