Efficacy and safety of Programmed Death Ligand 1 inhibitors versus Programmed Death 1 inhibitors in the first-line treatment of advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials
TL;DR
The combination of PD-1 inhibitors and chemotherapy may provide a significant OS and PFS benefit relative to PD-L1 inhibitors plus chemotherapy in NSCLC and a similar safety profile.
Abstract
Background With the increasing use of immune checkpoint inhibitors (ICIs) in the first-line treatment of driver mutation-negative non-small cell lung cancer (NSCLC), we conducted a systematic review and meta-analysis to compare efficacy and adverse effects (AEs) between PD-L1 inhibitors and PD-1 inhibitors. Methods We searched PubMed, Web of Science, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) related to the first-line treatment of NSCLC with ICIs alone or in combination with chemotherapy. The primary outcomes were overall survival (OS), progression-free survival (PFS), and AEs. Results In total, 28 RCTs involving 14,758 patients were included. Compared with Programmed Death 1 (PD-1) inhibitors plus chemotherapy, Programmed Death Ligand 1 (PD-L1) inhibitors plus chemotherapy were associated with worse OS (hazard ratio (HR) = 1.26; 95% confidence interval (CI) [1.13–1.41]; P < 0.001) and PFS (HR = 1.21; 95% CI [1.06–1.38]; P = 0.005). The objective response rate (ORR) did not differ between PD-1 inhibitors plus chemotherapy and PD-L1 inhibitors plus chemotherapy (odds ratio (OR) = 0.91; 95% CI [0.78–1.05], P = 0.205), and AE rates were similar between these groups. Regarding monotherapy, no difference in OS, PFS, or ORR was observed between PD-L1 and PD-1 inhibitors. The incidence of AEs leading to treatment termination and grade ≥3 AEs was lower for PD-L1 inhibitors than PD-1 inhibitors (risk ratio (RR) = 0.55; 95% CI [0.32–0.95]; P = 0.03; RR = 0.76; 95% CI [0.60–0.96]; P = 0.021). Conclusions The combination of PD-1 inhibitors and chemotherapy may provide a significant OS and PFS benefit relative to PD-L1 inhibitors plus chemotherapy in NSCLC and a similar safety profile. Meanwhile, PD-L1 inhibitor monotherapy appears less likely to result in treatment termination or grade ≥3 AEs than PD-1 inhibitor monotherapy.