Su Shiqing
Emergency Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Oncol Lett. 2023 Jul 17;26(3):373. doi: 10.3892/ol.2023.13960. eCollection 2023 Sep.
Although the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor combined with chemotherapy vs. chemotherapy alone has been analyzed, there have been no in-depth studies on the outcomes of patients with PD-L1 positive advanced gastric or gastro-esophageal junction cancer patients (GC/GEJC). This systematic review and meta-analysis focused on comparing the efficacy and safety of PD-1/PD-L1 inhibitors vs. PD-1/PD-L1 inhibitors combined with chemotherapy vs. chemotherapy in PD-L1 positive advanced GC/GEJC patients, aiming to provide more precise guidance for the clinical treatment of GC/GEJC. In this meta-analysis, PubMed, Embase, and Cochrane Library were searched from the establishment of the database till June 2022. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy and experimental group patients underwent PD-1/PD-L1 inhibitors or PD-1/PD-L1 inhibitors combined with chemotherapy were included in this investigation. Investigations without complete information, studies from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. The pooled results suggested that chemotherapy combined with immunotherapy prolonged overall survival (OS) in patients with advanced GC/GEJC, while progression free-survival (PFS) with PD-1/PD-L1 inhibitors alone or in combination with chemotherapy were all improved compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors did not significantly increase objective response rates (ORR) in PD-L1-positive patients compared with chemotherapy, but in combination with chemotherapy, they did improve ORR. The pooled results also showed that patients treated with PD-1/PD-L1 inhibitors had higher stable disease (SD) and progressive disease (PD) rates compared to chemotherapy in PD-L1-positive patients. Additionally, in PD-L1-positive patients, PD-1/PD-L1 inhibitors alone or combined with chemotherapy increased OS compared with chemotherapy alone. However, PD-1/PD-L1 inhibitors only prolonged PFS compared with chemotherapy alone in patients with a combined positive score (CPS; 100% of cells were required to be positively stained) for PD-L1, but when combined with chemotherapy, OS and PFS were prolonged in all PD-L1-positive patients compared with chemotherapy alone. Finally, the pooled results showed that the incidence of adverse events of PD-1/PD-L1 inhibitors in PD-L1-zpositive patients was significantly lower than that in patients treated with chemotherapy alone. In conclusion, single agent of PD-1/PD-L1 inhibitor alone or combined with chemotherapy significantly prolongs the survival of patients compared with chemotherapy alone, with fewer adverse effects. However, the degree of CPS may affect efficacy, thus further investigation is required.
尽管已分析了程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）抑制剂联合化疗与单纯化疗的疗效和安全性，但对于PD-L1阳性的晚期胃癌或胃食管交界癌（GC/GEJC）患者的治疗结局尚无深入研究。本系统评价和荟萃分析聚焦于比较PD-1/PD-L1抑制剂、PD-1/PD-L1抑制剂联合化疗与单纯化疗在PD-L1阳性晚期GC/GEJC患者中的疗效和安全性，旨在为GC/GEJC的临床治疗提供更精准的指导。在这项荟萃分析中，检索了从数据库建立至2022年6月的PubMed、Embase和Cochrane图书馆。本研究纳入了对照患者接受化疗而实验组患者接受PD-1/PD-L1抑制剂或PD-1/PD-L1抑制剂联合化疗的随机对照试验（RCT）。排除信息不完整的研究、无法提取信息的研究、重复文章、动物研究、综述文章和系统评价。汇总结果表明，化疗联合免疫疗法可延长晚期GC/GEJC患者的总生存期（OS），而单独使用PD-1/PD-L1抑制剂或联合化疗的无进展生存期（PFS）均较单纯化疗有所改善。然而，与化疗相比，PD-1/PD-L1抑制剂并未显著提高PD-L1阳性患者的客观缓解率（ORR），但联合化疗时可提高ORR。汇总结果还显示，在PD-L1阳性患者中，接受PD-1/PD-L1抑制剂治疗的患者的疾病稳定（SD）和疾病进展（PD）率高于化疗患者。此外，在PD-L1阳性患者中，单独使用PD-1/PD-L1抑制剂或联合化疗与单纯化疗相比可提高OS。然而，仅在PD-L1联合阳性评分（CPS；要求100%的细胞呈阳性染色）的患者中，PD-1/PD-L1抑制剂与单纯化疗相比仅延长了PFS，但与单纯化疗相比，联合化疗时所有PD-L1阳性患者的OS和PFS均延长。最后，汇总结果显示，PD-L1阳性患者中PD-1/PD-L1抑制剂的不良事件发生率显著低于单纯接受化疗的患者。总之，与单纯化疗相比，单独使用PD-1/PD-L1抑制剂或联合化疗可显著延长患者生存期，且不良反应较少。然而，CPS程度可能影响疗效，因此需要进一步研究。
