免疫检查点抑制剂联合化疗抗血管生成药物二线治疗晚期胃癌及胃食管结合部腺癌患者的疗效分析

Effect of immune checkpoint inhibitors combined with chemotherapy or antiangiogenic drugs as second-line treatment of advanced gastric cancer and gastroesophageal junction adenocarcinoma

背景 目前免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已成为晚期胃癌的一线及三线的标准治疗药物,但在二线治疗中仅被推荐用于伴有微卫星高度不稳定(MSI-H)或错配修复基因缺陷的患者,因此ICIs在晚期胃癌二线中的治疗模式需要更多的探索。目的 分析ICIs联合化疗、抗血管生成药物二线治疗晚期胃癌及胃食管结合部腺癌患者的疗效。方法 收集2018年6月-2022年1月在解放军总医院第一医学中心二线行ICIs联合化疗、抗血管生成药物治疗的晚期胃癌或胃食管结合部腺癌患者的临床资料,分析入组患者的中位无进展生存期(median progression-free survival,m PFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR)。采用Kaplan-Meier法绘制生存曲线,并使用Cox回归分析影响mPFS的预后因素。结果 本研究共纳入49例患者,其中男性34例,女性15例,中位年龄54岁。在二线治疗中,ICIs为纳武利尤单抗或信迪利单抗,27例患者应用纳武利尤单抗,22例应用信迪利单抗。28例患者联合以紫杉醇(白蛋白结合型)为主的方案,21例联合阿帕替尼,6例联合以铂类为主的方案,5例联合以伊立替康为主的方案。69.4%患者选择了免疫药物联合两种及以上抗肿瘤药物的治疗方案。全组患者的ORR为28.5%,DCR为89.8%,mPFS为4.7(95%CI:3.830~5.570)个月。多因素Cox分析示,无腹膜转移患者m PFS显著优于有腹膜转移患者(HR=0.410,95%CI:0.197~0.854, P=0.017),一线未应用免疫治疗患者的mPFS显著优于一线应用免疫治疗的患者(HR=0.518,95%CI:0.272~0.987,P=0.045),二线联合≥2种治疗药物患者的mPFS显著优于联合1种治疗药物的患者(HR=0.454,95%CI:0.231~0.890,P=0.021)。结论 晚期胃癌及胃食管结合部腺癌患者二线应用ICIs联合化疗、抗血管生成药物可能提高患者治疗的有效率,延长无进展生存时间。

Background Nowadays,immune checkpoint inhibitors(ICIs)have become standard first-line and third-line therapeutics in advanced gastric cancer.But in second-line therapy,they are only recommended for patients with microsatellite instability-high(MSI-H)or mismatch repair gene defects.Therefore,the treatment mode of ICIs in the second-line of advanced gastric cancer needs more exploration.Objective To analyze the efficacy of ICIs combined with chemotherapy and antiangiogenic drug in the treatment of advanced gastric cancer and gastroesophageal junction cancer.Methods Clinical data about patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma who received ICIs combined with chemotherapy and antiangiogenic drug in the second line of the First Medical Center of Chinese PLA General Hospital from June 2018 to January 2022 were collected.Median progression-free survival(mPFS),objective response rate(ORR)and disease control rate(DCR)of enrolled patients were analyzed.Kaplan-Meier method was used to plot the survival curve,and COX regression was used to analyze the prognostic factors affecting mPFS.Results A total of 49 patients with a median age of 54 years were included in this study,including 34 males and 15 females.In second-line therapy,ICIs were either nivolumab or sintilimab,with 27 patients receiving nivolumab and 22 patients receiving sintilimab.There were 28 patients combined with albumin bound paclitaxel,21 cases with apatinib,6 case with platinum-based regimen,and 5 case with irinotecan-based regimen.About 69.4%of the patients chose immuno-therapy combined with≥2 antitumor drugs.The ORR was 28.5%,DCR was 89.8%,mPFS was 4.7(95%CI:3.830-5.570)months.Multivariate Cox analysis showed that mPFS in patients without peritoneal metastasis was significantly better than that in patients with peritoneal metastasis(HR=0.410,95%CI:0.197-0.854,P=0.017);patients who did not receive first-line immunotherapy were signifi-cantly better than those receiving first-line immunotherapy(HR=0.518,95%CI:0.272-0.987,P=0.045),and patients with a second-line combination of≥2 drugs had significantly better PFS prognosis than those with a combination of one drug(HR=0.454,95%CI:0.231-0.890,P=0.021).Conclusion ICIs combined with chemotherapy or antiangiogenic drugs as second-line therapy may improve the effective rate and prolong the PFS of patients with advanced gastric cancer and gastroesophageal junction adenocarcinoma.