Anti PD-1 (nivolumab, pembrolizumab) or anti PD-L1 (atezolizumab) versus docetaxel for previously treated patients with advanced NSCLC: A meta-analysis.

BACKGROUND: In phase I studies, Immune Checkpoint Inhibitors (ICIs) targeting programmed death protein 1 (PD-1) receptor and its ligand, PD-L1, have recently led to significant efficacy in advanced NSCLC in second and more lines setting. We undertook a meta-analysis of all published randomized studies in this setting to assess the range of improvements. METHODS: We did a PubMed query using keywords simultaneously (NSCLC, anti PD-1, anti PDL-1, docetaxel, survival, and RCTs). We also screened ASCO and ESMO proceedings. The efficacy outcomes were OS, response rate and PFS. Grade 3-5 toxicity was also examined. Hazard ratios (HRs) with their 95 % confidence interval (CI) were collected from the studies and pooled. A fixed-effect model was used. RESULTS: Two studies assessed nivolumab (CheckMate 017 and 057), one atezolizumab (Poplar), and one pembrolizumab (Keynote 010). The four eligible studies included 2174 patients (1330 males, 844 females, mostly smokers (81%), median age 62 years), with 1496 nonsquamous (69 %) and 591 squamous tumours (27%). The risk of death was 32% lower with ICIs than with docetaxel (HR = 0.68, 95 % CI 0.61-0.75, p < 0.00001). Improvements in OS were observed with both squamous and non-squamous tumours (HR = 0.67, 95% CI 0.54-0.82 and HR = 0.63, 95% CI 0.53-0.74 respectively). The response rate was 18% with ICIs versus 10% with docetaxel (P = 0.008). ICIs were associated with significant PFS improvement compared with docetaxel (HR = 0.84, 95% CI 0.77-0.92; P = 0.0002). In patients with PDL-1 positive cancer ( > 1% or > TC0/IC0), OS and PFS benefits were statistically significant (HR = 0.64, 95% CI 0.57-0.71 and HR = 0.80, 95% CI 0.72-0.88 respectively) when they were not statistically significant in patients with PDL-1 negative cancer ( < 1% or = TC0/IC0), (HR = 0.83, 95% CI 0.66-1.04 and HR = 1.01, 95% CI 0.81-1.25 respectively). Treatment-related adverse events of grade 3-5 were reported in 12% of the patients in the ICIs group as compared with 42% of those in the docetaxel group. CONCLUSIONS: Among patients with advanced, previously treated PDL-1 positive NSCLC, OS, response rate, and PFS were significantly better with ICIs than with docetaxel.