OBJECTIVES: To assess the efficacy and safety of PD-1/PDL-1 (Programmed cell death protein 1/ Programmed death-ligand 1) inhibitors in previously treated advanced/metastatic NSCLC

METHODS: We searched PubMed, Cochrane libraries, and ClinicalTrials.gov databases for the identification of RCTs comparing approved PD-1 inhibitors and anticancer treatments. ASCO, ESMO, and ISPOR were also searched for relevant abstracts. The search strategy comprised of PD-1/PDL-1 drugs and non-small cell lung cancer. The primary outcomes of interest were overall survival (OS), Progression free survival (PFS), and overall response rate (ORR). Two reviewers independently conducted the screening, data abstraction, and the quality assessment. Heterogeneity was assessed using the chi-square test.

RESULTS: A total of three RCTs evaluating PD-1/PDL-1 (pembrolizumab, nivolumab, and atezolizumab) and 2803 patients with advanced NSCLC were included in this network meta-analysis. The pooled results indicated no significant difference between pembrolizumab (2 mg/kg & 10 mg/kg), atezolizumab (RR: -0.01; 95%CI: -17.4-17.1), and nivolumab (RR: 1.36; 95%CI: -16.11 – 18.79) for OS. Similarly there was no significant difference for PFS and the respective values were: atezolizumab (RR: 1.19, 95%CI: -16.38-18.47), and nivolumab (RR: 1.86; 95%CI: -15.59 – 19.63). No statistically significant differences were observed in case of ORR as well. However, pembrolizumab 10 mg/kg showed numerically higher values compared to pembrolizumab 2 mg/kg and other PD-1 drugs. All treatments were equally tolerable in terms of adverse events and serious adverse events. Most commonly reported adverse events were decreased appetite, fatigue, dysponea, and nausea. All included clinical trials demonstrated high quality.

CONCLUSIONS: Our findings demonstrated that pembrolizumab (2 mg & 10 mg/kg), atezolizumab, and nivolumab are equally efficacious and have similar safety profile in previously treated advanced and metastatic NSCLC patients.