Pan-tumour analysis of the association between PD-L1 combined positive score (CPS) and response to pembrolizumab monotherapy

Abstract

PD-L1 is expressed on tumour and immune cells; PD-L1 CPS captures tumour and immune cell expression in one aggregate score. We performed a retrospective, exploratory analysis of CPS as an enrichment biomarker of pembrolizumab monotherapy across multiple tumour types. PD-L1 expression was assessed using PD-L1 IHC 22C3 pharmDx and measured using CPS (number of PD-L1-staining cells [tumour cells, lymphocytes, macrophages] divided by total number of tumour cells, multiplied by 100). Data were pooled from 11 studies across tumour types for pembrolizumab and for standard-of-care (in controlled studies). Estimates of ORR, prevalence, and receiver operating characteristics (ROC) analysis was performed over various CPS cut-points. CPS distribution by response, tumour type, and line of therapy were also assessed. 3769 patients had available PD-L1 CPS (pembrolizumab, n=2678; standard-of-care, n=1091). Area under the ROC curve for ORR was 0.63 (95% CI, 0.61–0.66; pembrolizumab) versus 0.48 (95% CI, 0.43–0.53; standard-of-care); cut-points of 1, 10, 20, and 50 were also examined. This pan-tumour analysis demonstrates that CPS is an effective method for scoring PD-L1 expression and can be used as a predictive biomarker to identify patients likely to respond to pembrolizumab monotherapy. CPS demonstrated enrichment of response to pembrolizumab monotherapy across most tumour types.