PD-L1 status and efficacy of immune check-point inhibitors (ICIs) in advanced cancer patients: A pooled analysis of randomized trials.

Abstract

e15263 Background: The introduction of immune check-point inhibitors (ICIs) in the treatment of a broad range of tumor types has led to a significant and clinically meaningful improvement in overall survival (OS) in advanced disease stages. However, the efficacy of these agents is not consistent across trials and in routine practice. The role of PD-L1 expression as a tumour-agnostic predictive correlate of response to ICIs remains unclear. We performed a pooled analysis of the efficacy of PD-1/PD-L1-targeted ICI regimens as compared to standard of care (SoC) therapy according to PD-L1 expression, based on landmark clinical studies. Methods: We searched literature databases to identify phase III randomized controlled trials that compared anti-PD-1/PD-L1 antibodies alone or in combination with chemotherapy or targeted agents against SoC therapy in the treatment of different tumor types. We reported efficacy data, in terms of OS, according to PD-L1 status. Log hazard ratios (HRs) were pooled across the studies overall and by PD-L1 status by inverse variance weighting. All statistical tests were two-sided. Results: Twenty-four studies including 17687 randomised patients with advanced lung, renal, urothelial, liver, breast, head and neck cancers and melanoma, were eligible for analysis. Efficacy according to PD-L1 immunohistochemical expression, with a 1% cutoff ( < 1% versus > 1%), was reported in 11 studies (7126 patients). Overall, ICI-containing regimes were significantly superior in terms of OS to SoC regimens (pooled HR = 0.64; 95% CI 0.60 to 0.68). When OS data were pooled according to PD-L1 expression, HR was 0.66; 95% CI 0.61 to 0.71 in PD-L1 < 1%, versus 0.62; 95% CI 0.56 to 0.68 in PD-L1 >1% (p = 0.7). Conclusions: The significant improvement in OS favoring the use of ICIs over SoC does not seem to be confined to patients with PD-L1-overexpressing tumours. The difference in efficacy according to PD-L1 status appears to be, at best, marginal.