1199P - Clinical and molecular characteristics associated with efficacy of PD-1/PD-L1 inhibitors for solid tumors: A meta-analysis

Abstract

Background: In the new era of precision medicine, identifying clinical or molecular factors that predict benefit of immune checkpoint inhibitors is crucial to prevent patients from autoimmune adverse effects and high cost of such agents. Methods: We conducted this meta-analysis on the basis of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Two reviews independently completed a search of PubMed and Web of science to identify relevant clinical trials. The search was conducted using keywords “nivolumab”, “pembrolizumab”, “atezolizumab” and “immune checkpoint”. The search was limited to randomized controlled trails (RCTs) published in English. Results: Eleven eligible studies, including 5,663 patients, were included in this meta-analysis. In our analysis, PD-1/PD-L1 inhibitor was associated with a 31% reduction in the risk of death (HR = 0.69; 95%CI, 0.64-0.74; P < 0.00001). In subgroup analysis, patients got overall survival (OS) benefit from PD-1/PD-L1 inhibitors regardless of PD-L1 expression, and a dose effect relationship between expression of PD-L1 and OS benefit from PD-1/PD-L1 inhibitors was observed (Interaction, P < 0.00001). Patients with smoking history achieved greater OS benefits (HR = 0.69, 95% CI 0.61-0.77; P < 0.00001) than never smoker (HR = 0.88, 95% CI 0.70-1.11; P = 0.28). Compared with second or later line treatment, there was better OS benefits in first line treatment subgroup (Interaction, P = 0.02). The OS benefits were similar according to age (Interaction, P = 0.74), sex (Interaction, P = 0.43), performance status (Interaction, P = 0.68), central nervous system (CNS) metastasis (Interaction, P = 0.59), tumor histology (Interaction, P = 0.64) and treatment type (Interaction, P = 0.36). Conclusions: In conclusion, PD-L1 expression, smoking status and line of treatment were potential biomarkers for PD-1/PD-L1 inhibitors. Besides, patients > 75 years of age might not get OS benefits from this treatment. These results may improve treatment strategies and patient selection for PD-1/PD-L1 inhibitors. Legal entity responsible for the study: Y. Weng. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.