OBJECTIVES: Since the efficacy of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor monotherapy (PD1-mono) correlates with PD-L1 expression levels, a meta-analysis was conducted to assess the efficacy of first-line PD1-mono vs platinum chemotherapy in patients with different PD-L1 expression levels.

METHODS: PubMed, Embase, Scopus and ClinicalTrials.gov were systematically searched through March 2021 to identify randomized controlled trials (RCTs) comparing PD1-mono and platinum chemotherapy as first-line treatment of advanced NSCLC. A meta-analysis using random-effects models was performed to assess overall survival (OS) and progression-free survival (PFS) among patients with ≥1%, ≥50%, and 1-49% PD-L1 expression levels using Comprehensive Meta Analysis software.

RESULTS: 4,860 patients from eight RCTs were included in the study. Among patients with PD-L1 levels ≥1% (6 RCTs; 3,992 patients), PD1-mono was associated with better OS (hazard ratio [HR]: 0.858; 95% CI: 0.779, 0.945; p-value: 0.002) and similar PFS (HR: 1.010; 95% CI: 0.905, 1.128; p-value: 0.857) compared to chemotherapy. PD-L1 levels ≥50% were associated with significantly better OS (7 RCTs; 2,257 patients; HR: 0.675; 95% CI: 0.559, 0.760; p-value <0.001) and PFS (6 RCTs; 2,032 patients; HR: 0.701; 95% CI: 0.558, 0.880; p-value: 0.002) with PD1-mono treatment. While patients with PD-L1 levels of 1-49% had comparable OS with either PD1-mono or chemotherapy (3 RCTs; 945 patients; HR: 0.897; 95% CI: 0.766, 1.051; p-value: 0.179), there was a trend toward improved PFS with chemotherapy treatment (2 RCTs; 829 patients; HR: 1.199; 95% CI: 0.981, 1.465; p-value: 0.076).

CONCLUSION: Analysis of patients with PD-L1 levels of 1-49% suggests that the OS benefit among patients with PD-L1 levels ≥1% may be attributed to patients with PD-L1 levels ≥50%. Further study is necessary to better understand the value of PD1-mono treatment in patients with PD-L1 levels <50%.