Lee CK, et al. - Researchers aimed at estimating the relative efficacy of checkpoint inhibitor vs docetaxel overall and in subgroups defined by clinicopathological characteristics for advanced non–small cell lung carcinoma (NSCLC). In this study, compared with docetaxel, checkpoint inhibitors were associated with significantly prolong overall survival in second-line therapy in NSCLC. Patients with EGFR mutant tumors indicated no overall survival benefit suggesting to consider checkpoint inhibitors only after other effective therapies have been exhausted.

Methods

• For this systematic review and meta-analysis, researchers searched MEDLINE, Embase, PubMed, and the Cochrane Central Register of Controlled Trials for randomized clinical trials published in the English language from January 1, 1996 to January 30, 2017.
• They selected randomized clinical trials comparing a checkpoint inhibitor (nivolumab, pembrolizumab, or atezolizumab) with docetaxel.
• They extracted the trial name, year of publication or conference presentation, patients’ clinicopathological characteristics, type of chemotherapy, and type of checkpoint inhibitor for each trial included in this study.
• Data collection was performed from February 1 to March 31, 2017 for this study.
• Study selection, data abstraction, and risk of bias assessment were performed by 2 reviewers.
• For the overall population and subgroups, they extracted hazard ratios (HR) and 95% CIs.
• they used the inverse-variance-weighted method to calculate the pooled treatment estimates.

Results

• This meta-analysis included in total, 5 trials involving 3,025 patients with advanced NSCLC.
• Randomization of these patients to receive a checkpoint inhibitor (nivolumab, 427 [14.1%]; pembrolizumab, 691 [22.8%]; or atezolizumab, 569 [18.8%]) or docetaxel (1338 [44.2%]) was performed.
• Checkpoint inhibitors compared with docetaxel were correlated with prolonged overall survival (HR, 0.69; 95% CI, 0.63-0.75; P < .001).
• The prolonged overall survival was observed in the EGFR wild-type subgroup (HR, 0.67; 95% CI, 0.60-0.75; P < .001), but not in the EGFR mutant subgroup (HR, 1.11; 95% CI, 0.80-1.53; P=.54; interaction, P=.005), and the prolonged overall survival was evident in the KRAS mutant subgroup (HR, 0.65; 95% CI, 0.44-0.97; P=.03) but not in the KRAS wild-type subgroup (HR, 0.86; 95% CI, 0.67-1.11; P=.24; interaction, P=.24).
• Data revealed that the relative treatment benefits were comparable in accordance to smoking status (never smokers [HR, 0.79] vs ever smokers [HR, 0.69]; interaction, P=.40), performance status (0 [HR, 0.69] vs 1 [HR, 0.68]; interaction, P=.85), age (<65 years [HR, 0.71] vs ≥65 years [HR, 0.69]; interaction, P=.74), histology (squamous [HR, 0.67] vs nonsquamous [HR, 0.70]; interaction, P=.71), or sex (male [HR, 0.69] vs female [HR, 0.70]; interaction, P=.82).