The efficacy and potential predictive factors of PD-1/PD-L1 blockades in epithelial carcinoma patients: a systematic review and meta analysis

BACKGROUND: This systematic analysis aims to assess the efficacy of PD-1/PD-L1 blockades compared with non-PD-1/PD-L1 therapy and investigate the potential predictive factors in epithelial carcinoma patients. RESULTS: A total of 11 trials with 6716 patients of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were included. The pooled HRs (95%CI) were 0.67 (0.62, 0.73), p < 0.001 for OS and 0.66 (0.57, 0.76), p < 0.001 for PFS. In subgroup analyses, HRs were 0.58 (0.50, 0.66), p < 0.001 in PD-L1 ≥ 1% group, 0.75 (0.63, 0.89), p = 0.001 in PD-L1 < 1% group for OS and 0.59 (0.48, 0.72), p < 0.001 in PD-L1 ≥ 1% group, 0.80 (0.59, 1.07), p = 0.136 in PD-L1 < 1% group for PFS. The p values of pooled HRs for OS in different age, sex and ECOG score groups were less than 0.001. In NSCLC patients, aggregated HRs for OS were 1.40 (0.92, 2.12), p = 0.114 in EGFR mutant group and 0.88 (0.59, 1.32), p = 0.536 in never smokers. METHODS: A systematic search from January 2010 to April 2016 was conducted for eligible clinical trials. Based on the data of hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS), we assessed the pooled HRs and proposed the subgroup analyses. CONCLUSIONS: PD-1/PD-L1 blockades prolonged OS and PFS in epithelial carcinoma patients. PD-L1 expression was a predictive factor for PFS but not predictive for OS. Age, sex and ECOG score were excluded to predict any of the efficacy endpoints. Smoking history and EGFR wild type were associated with extended OS in NSCLC patients.