晚期胃癌免疫治疗再挑战的临床分析

Clinical analysis of immunotherapy rechallenge in advanced gastric cancer

目的:探讨程序性死亡受体1(PD-1)单抗再挑战治疗在晚期胃癌中的临床疗效及影响因素。方法:回顾性收集2020年1月至2021年12月就诊河南省肿瘤医院使用PD-1单抗再挑战治疗晚期胃癌患者的临床资料。初次或再次使用PD-1单抗治疗开始至疾病进展或末次随访日期的时间为无进展生存时间(PFS),分别命名为PFS 1和PFS 2,生存分析采用Kaplan-Meier法和Log rank检验,预后影响因素分析采用Cox比例风险模型。结果:60例PD-1单抗再挑战治疗患者的中位随访时间为12.2个月,中位PFS 2为2.9个月,客观缓解率(ORR)为16.7%,疾病控制率(DCR)为55.0%。首次及再次使用相同PD-1单抗和不同PD-1单抗挑战治疗的中位PFS 2分别为3.5和1.9个月(P=0.007)。再挑战治疗中程序性死亡受体配体1表达阳性患者的中位PFS 2为3.4个月,ORR为22.7%,DCR为63.6%;中位PFS 1≥6个月患者的中位PFS 2为4.5个月,ORR为27.3%,DCR为54.5%。多因素分析显示,腹膜转移是PD-1单抗再挑战治疗PFS 2的独立影响因素(HR=2.327,95%CI:1.066~5.082,P=0.034)。PD-1单抗再挑战治疗中1~2级不良反应发生率为83.3%(50/60),3~4级为35.0%(21/60),安全性可控。结论:晚期胃癌中PD-1单抗再挑战治疗是一种可行的治疗方式,但再挑战治疗适宜人群的筛选仍需前瞻性数据分析验证。

ObjectiveTo evaluate the efficacy and influencing factors of programmed death protein 1(PD-1)monoclonal antibody rechallenge therapy in advanced gastric cancer(GC).MethodsThe clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively.The progression-free survival(PFS)was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up,named PFS1 and PFS 2,respectively.Kaplan-Meier method and Log rank test were used for survival analysis,Cox proportional hazard model was used to analyze the influencing factors.ResultsA total of 60 patients with anti-PD-1 rechallenge therapy were collected,the median follow-up time was 12.2 months.The median progression-free survival(PFS2)of anti-PD-1 rechallenge therapy was 2.9 months,the objective response rate(ORR)was 16.7%,and the disease control rate(DCR)was 55.0%.The median PFS2 of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months(P=0.007)respectively.The median PFS2 of positive PD-L1 expression in rechallenge therapy was 3.4 months,ORR was 22.7%,and DCR was 63.6%;the median PFS2 was 4.5 months,ORR was 27.3%,and DCR was 54.5%in patients with median PFS1≥6 months.Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS2(HR=2.327,95%CI,1.066-5.082,P=0.034).The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%,and 35.0%,respectively,and the safety was controllable.ConclusionRechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC,but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.