Correlation between PD-L1 expression and outcome of NSCLC patients treated with anti-PD-1/PD-L1 agents: A meta-analysis

Background: A meta analysis of the correlation between PD-L1 levels and outcomes of PD-1/PD-L1 inhibitors in advanced non small cell lung cancer (NSCLC) has been performed. Methods: Eligible studies included those evaluating PD-1/PD-L1 inhibitors in advanced NSCLC and correlating the outcomes to PD-L1 levels. Results: The search strategy yielded 250 potentially relevant citations from searched databases. After preclusion of ineligible studies, 12 studies were included. Comparing PD-1/PD-L1 inhibitors to docetaxel in second line treatment, the pooled hazard ratio (HR) for progression free survival (PFS) and overall survival (OS) was 0.75 (95% CI 0.62-0.90; p = 0.002) and 0.61 (95% CI 0.50-75; p = 0.00001) respectively; while the pooled odds ratio (OR) for objective response rate (ORR) was 1.98 (95% CI 1.28-3.07; p = 0.002) in the PD-L1 > 1% population. Moreover, for PD-L1 > 1% patients versus PD-L1 < 1% patients treated with PD-1/PD-L1 targeted agents, the OR of ORR was 2.18 (95% CI 1.45-3.29; p = 0.0002); while for PD-L1 > 5% patients versus PD-L1 < 5% patients, it was 2.66 (95% CI 1.74-4.07; p < 0.00001); and for PD-LI > 10% versus PD-L1 < 10% patients, it was 3.38 (95% CI 2.23-5.13; p < 0.00001); and for PD-L1 > 50% versus PD-L1 < 50% patients, it was 3.99 (95% CI 2.81-5.66; p < 0.00001). Conclusions: The current analysis of data indicates that the benefit from PD-1 inhibitors versus docetaxel in second line treatment of NSCLC is limited to the PD-L1 >1% subpopulation. Moreover, a possible dose effect relationship between the intensity of PD-L1 staining and the potential benefit from PD-1/PD-L1 targeted agents does exist with higher intensity associated with higher ORR. (C) 2016 Elsevier Ireland Ltd. All rights reserved.