目的:系统评价皮肤免疫相关不良事件(cirAEs)与PD-1/PD-L1治疗非小细胞肺癌(NSCLC)疗效的关系,为PD-1/PD-L1的临床应用及安全性评价提供循证参考。
方法:电子数据库(PubMed,Embase,Medline,WebofScience,和Cochrane库)进行了系统筛选,以收集有关cirAEs与PD-1/PD-L1治疗NSCLC疗效之间相关性的前瞻性或回顾性队列研究。
结果:共有3514名参与者被纳入13项队列研究(包括一项双向队列研究)。结果显示,与那些无cirAE的患者相比,患有cirAE的患者与显著较高的客观缓解率(ORR)[风险比(RR):1.74,95%置信区间(CI):1.42-2.14,P<0.00001]相关,无进展生存期(PFS)[RR:0.52,95%CI:0.45-0.60,P<0.00001],和更长的总生存期(OS)[RR:0.46,95%CI:0.38-0.56]。通过一次排除一项研究的敏感性分析对结果没有显着影响,表明荟萃分析结果相对稳健。此外,亚组分析显示研究设计的结果一致(前瞻性或回顾性队列研究),以及可评估患者的Kaplan-Meier曲线或Cox比例风险回归的终点结果(PFS和OS)。
结论:目前,证据显示,cirAEs的发生可能与良好的预后相关,并且可以作为PD-1/PD-L1治疗NSCLC患者疗效的早期预测指标.
OBJECTIVE: To systematically evaluate the relationship between cutaneous immunerelated adverse events (cirAEs) and the efficacy of PD-1/PD-L1 in the treatment of non-small cell lung cancer (NSCLC) and to provide an evidence-based reference for the clinical application of PD-1/PD-L1 and safety evaluation.
METHODS: Electronic databases (PubMed, Embase, Medline, Web of Science, and the Cochrane Library) were screened systematically to collect prospective or retrospective cohort studies on the correlation between cirAEs and efficacy of PD-1/PD-L1 in the treatment of NSCLC.
RESULTS: A total of 3514 participants were included in 13 cohort studies (enclosing an ambidirectional cohort study). Outcomes revealed that compared with those patients with non cirAEs, patients suffering cirAEs were associated with significantly higher objective response rate (ORR) [risk ratio (RR): 1.74, 95% confidence interval (CI): 1.42-2.14, P<0.00001], longer progressionfree survival (PFS) [RR: 0.52, 95% CI: 0.45-0.60, P<0.00001], and longer overall survival (OS) [RR:0.46, 95% CI: 0.38-0.56]. Sensitivity analyses through the exclusion of one study at a time did not significantly influence the outcomes, indicating that the meta-analysis results were relatively robust. Furthermore, subgroup analyses revealed consistent results in the study design (prospective or retrospective cohort studies), as well as in the endpoint results (PFS and OS) of Kaplan-Meier curves or Cox proportional hazards regression for evaluable patients.
CONCLUSIONS: Currently, evidence reveals that cirAEs development may be associated with a good prognosis and can be an early predictor of the efficacy of PD-1/PD-L1 in the treatment of NSCLC patients.