Comparative analysis of immune checkpoint inhibitors and chemotherapy in the treatment of advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Abstract

Background: Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC.

Methods: A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science. Hazard ratios or odds ratios obtained for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment related adverse events (TRAEs) were analyzed using fixed effect model or random effects model. Additionally, subgroup analysis was also performed.

Results: A total of seven RCTs (n = 3867) were identified and selected for inclusion in this meta-analysis. Anti-PD1/PD-L1 therapies (nivolumab, pembrolizumab, atezolizumab) resulted in better OS (HR 0.72 [95% confidence interval [CI] 0.63, 0.82; P < .00001]), PFS (HR 0.84 [95% CI 0.72, 0.97; P < .02]), and ORR (odds ratio [OR] 1.52 [95% CI 1.08, 2.14; P < .02]) in comparison to chemotherapy in advanced NSCLC. Improved safety was observed with anti-PD1/PD-L1 therapies (OR 0.31 [95%CI 0.26, 0.38; P < .00001]). Subgroups analysis revealed Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (HR 0.76 [95%CI 0.62, 0.93; P = .007]), squamous cell type (HR 0.76 [95% CI 0.63, 0.92; P = .005]), current/former smoker (HR 0.76 [95% CI 0.63, 0.92; P = .005]), epidermal growth factor receptor (EGFR) wild type (HR 0.67 [95% CI 0.60, 0.76; P < .00001]), Kirsten rat sarcoma oncogene mutation (KRAS) mutant (HR 0.60 [95% CI 0.39, 0.93; P < .02]), and absence of central nervous system (CNS) metastases (HR 0.71 [95% CI 0.63, 0.80; P < .00001]) were associated with better overall survival.

Conclusions: Anti-PD1/PD-L1 therapies are safe and effective treatment option in advanced non-small cell lung cancer and can be recommended selectively.

Figure 1

The flow diagram of literature search and selection process.

Figure 2

Risk of bias graph. +: low risk of bias; −: high risk of bias; ?: unclear risk of bias.

Figure 3

Risk of bias summary.

Figure 4

Forest plot of meta-analysis of the overall survival (OS) showing comparison of anti-PD1/ PD-L1 therapy to chemotherapy in advanced NSCLC. NSCLC = non-small cell lung cancer; PD-1 = programmed cell death-1; PD-L1 = programmed cell death ligand 1.

Figure 5

Forest plot of meta-analysis of the progression-free survival (PFS) showing comparison of anti-PD1/ PD-L1 therapy to chemotherapy in advanced NSCLC. NSCLC = non-small cell lung cancer; PD-1 = programmed cell death-1; PD-L1 = programmed cell death ligand 1.

Figure 6

Forest plots of subgroup analysis of association between overall survival (OS) and PD-L1 tumor expression level at cut off values of 1%, 5%, 10%, and 50%. PD-L1 = programmed cell death ligand 1.

Figure 7

Forest plots of subgroup analysis of association between progression-free survival (PFS) and PD-L1 tumor expression level at cut off values of 1%, 5%, 10%, and 50%. PD-L1 = programmed cell death ligand 1.

Figure 8

Forest plot of meta-analysis of the objective response rate (ORR) showing comparison of anti-PD1/PD-L1 therapy to chemotherapy in advanced NSCLC. NSCLC = non-small cell lung cancer; PD-1 = programmed cell death-1; PD-L1 = programmed cell death ligand 1.

Figure 9

Forest plot of meta-analysis of the overall and Grade ≥ 3, 4, or 5 treatment-related adverse events (TRAEs) showing comparison of anti-PD1/ PD-L1 therapy to chemotherapy in advanced NSCLC. NSCLC = non-small cell lung cancer; PD-1 = programmed cell death-1; PD-L1 = programmed cell death ligand 1.

Figure 10

Forest plot of meta-analysis of the overall incidence rates of treatment-related adverse events (TRAEs) showing comparison of anti-PD1/PD-L1 therapy to chemotherapy in advanced NSCLC. NSCLC = non-small cell lung cancer; PD-1 = programmed cell death-1; PD-L1 = programmed cell death ligand 1.