Abstract 3720: Biological and clinical relevance of PD-L1 expression in tumor and inflammatory cells in NSCLC

Abstract

Abstract Background: High PD-L1 expression has been shown to be associated with improved clinical outcomes to anti-PD-1/L1 therapies in NSCLC and other indications. However, only a fraction of the PD-L1 high patients (pts) respond. PD-L1 can be induced by IFNG and expressed in tumor cells (TC) and inflammatory cells (IC). Improving our ability to predict patient benefit from anti-PD-1/L1 therapies requires a better understanding of associations between PD-L1 expression in TC and/or IC and outcome. Here we explore the relationship between patterns of IHC PD-L1 expression in TC and IC, gene expression, and clinical outcome. Methods: CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating durvalumab in pts with advanced NSCLC or other solid tumors. As of 29 APR 2016, 368 previously treated NSCLC pts received durvalumab ≤12 months with a median 18.8 months follow up. Pts with ≥25% TC or IC were scored TC+ and/or IC+, respectively. Results: TC+ PD-L1 pts (includes IC+ and IC- PD-L1 pts) had improved survival compared to TC- PD-L1 pts. TC+ and IC+ PD-L1 pts had: improved survival compared to TC+/IC-, TC-/IC+, or TC-/IC- PD-L1 pts. However, prevalence of TC+/IC+ was lower than TC+. Twenty-one genes significantly differed between TC+/IC+, TC+/IC-, TC-/IC+, and TC-/IC- PD-L1 patient subsets, the vast majority being well-known IFNG-inducible genes and mostly over-expressed in the TC+/IC+ subset. Conclusions: TC+ and IC+ PD-L1 pts had the highest levels of IFNG-inducible gene expression, a key biological feature that distinguishes PD-L1 IHC positive from negative pts. Thus, in addition to PD-L1 IHC, the predictive value of IFNG should be investigated in additional relevant studies Selection CriteriaPrevalence of Biomarker Positive BiomarkerPositive/negative median OSlog-rank pHRcox pTC+158/276 (57%)15.67/7.730.00910.690.046TC+/IC+70/276 (25%)25.63/8.377.46E-060.345.24E-05TC+/IC-88/276 (32%)10.5/13.970.0941.50.032TC-/IC+50/276 (18%)9.07/13.230.830.960.84TC-/IC-68/276 (25%)5.77/14.030.000841.660.012 All comers: median OS: 11.2 months (N=304) Citation Format: Carlos Bais, Chris Morehouse, Brandon W. Higgs, Rebelatto Marlon, Keith Steele, Xiaoping Jin, Li Shi, Susana Korolevich, Ashok Gupta, Koustubh Ranade. Biological and clinical relevance of PD-L1 expression in tumor and inflammatory cells in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3720. doi:10.1158/1538-7445.AM2017-3720