PD-1/PD-L1抑制剂在晚期胃癌治疗中的临床研究进展

Clinical research progress of PD-1/PD-L1 checkpoint inhibitors in advanced gastric cancer

胃癌是当今严重危害人类健康的恶性肿瘤之一,在中国多数胃癌患者在诊断时已接近晚期。虽然联合化疗仍为晚期胃癌的标准治疗方案,但其疗效未见显著改善。PD-1(programmed death 1)/PD-L1(programmed death ligand 1)免疫靶点治疗,阻断了肿瘤细胞逃离免疫机制,同时使T细胞活化增强,最终达到免疫杀伤肿瘤细胞的目的。截至目前,免疫检查点抑制剂在上消化道恶性肿瘤的临床研究中取得较好的结果,预示着PD-1/PD-L1抑制剂可能成为继标准化疗之后新一代治疗晚期胃癌的方案。目前已有研究表明,PD-1抑制剂Nivolumab及Pembrolizumab能客观缓解一些实体瘤,且这2个抑制剂已获美国FDA批准分别用于晚期鳞状非小细胞肺癌及不可切除/转移的黑色素瘤等肿瘤的临床治疗。多项PD-1/PD-L1抑制剂单药/联合化疗治疗晚期胃癌的临床研究正在进行,其中多数研究的总生存期及客观生存率等结论令人鼓舞。本文对免疫治疗中的PD-1/PD-L1通路抑制剂在晚期胃癌治疗中的临床研究进展进行综述。

Gastric cancer（GC） is one of the malignant tumors,which has a serious threat to human health. In China in particular,the vast majority of GC patients present with advanced-stage disease. Even though combination chemotherapy is still the most considerable component of treatment for advanced GC patients,it confers a modest survival advantage. PD-1/PD-L1 signaling pathway contributes to the anti-tumor effect of T cells,which can achieve the goal of killing tumor cells by inhibiting the tumor immune escape. With the further understanding of immune checkpoint inhibitors,such as PD-1/PD-L1 checkpoint inhibitors have been developed for treatment of solid tumors. Recently,the checkpoint inhibitors seems show some uplifting outcomes in upper gastrointestinal malignancy,and the PD-1/PD-L1 checkpoint inhibitors may also provide new therapeutic avenues in advanced gastric cancer. According to a number of convincing outcomes,some of these checkpoint inhibitors such as Nivolumab and Pembrolizumab even have changed the treatment paradigm for some solid tumors. As known to all,FDA has approved the Nivolumab,for the treatment of advanced squamous-cell NSCLC and Pembrolizumab for the treatment of unresectable/refractory melanoma. Meanwhile a lot of clinical trials of PD-1/PD-L1 checkpoint inhibitor monotherapy or combination chemotherapy for patients with advanced gastric cancer have been carried out and most of them perform well,so far as OS（overall survival） and ORR（objective response rate） are concerned overall. This review summarizes the clinical advancements in the targeted therapy with PD-1/PD-L1 checkpoint inhibitors in advanced gastric cancer.