Anti-PD-1/PD-L1 Antibody Therapy for Pretreated Advanced or Metastatic Nonsmall Cell Lung Carcinomas and the Correlation between PD-L1 Expression and Treatment Effectiveness: An Update Meta-Analysis of Randomized Clinical Trials

Abstract

Purpose. This meta-analysis systematically evaluated the efficacy and safety of anti-PD-1/PD-L1 antibodies for pretreated advanced or metastatic nonsmall cell lung cancer (NSCLC) and investigated the correlation between PD-L1 expression levels and effectiveness of anti-PD-1/PD-L1 antibody. Methods. The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and the Cochrane Collaboration guidelines. Results. Our research included five randomized-controlled trials involving 3,025 patients. We compared anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, and atezolizumab) with docetaxel in pretreated patients with advanced or metastatic NSCLC. The pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was 0.69 (95%CI: 0.63-0.75, P<0.0001, and Ph=0.67) and 0.87 (95%CI: 0.81-0.94, P=0.0004, and Ph=0.11), respectively. Meanwhile, the pooled risk ratio (RR) for objective response rate (ORR) was 1.53 (95% CI: 1.16-2.01, P=0.003, and Ph=0.03) in all patients. Subgroup analyses showed that anti-PD-1/PD-L1 treatment significantly improved OS in patients with PD-L1 expression at any level, even in patients with PD-L1<1%. The RR for occurrence of grades 3 to 5 treatment-related adverse effects was 0.23 (95% CI: 0.15-0.36, and P<0.001). Conclusion. OS, PFS, and ORR were significantly more improved for patients treated with anti-PD-1/PD-L1 antibodies than for those treated with docetaxel. Anti-PD-1/PD-L1 therapy resulted in longer OS than docetaxel, regardless of PD-L1 expression; however, higher PD-L1 levels were likely to correlate with better outcome. Anti-PD-1/PD-L1 antibodies also had a better safety profile than docetaxel.