Abstract 2657: Immune checkpoint status does not impact overall survival in NSCLC
Authors: Watza Donovan , Murphy Valerie , Lusk Chrissy , Wenzlaff Angie S. , Fulvio Lonardo , Neslund-Dudas Christine , Bepler Gerold , Schwartz Ann G. 
Published: August 2018

Abstract
Checkpoint blockade has altered standard of care for non-small cell lung cancer (NSCLC) expressing PD-L1, with trials demonstrating favorable prognosis in patients whose tumors were PD-L1 positive and were subsequently paired with anti-PD-1 therapy. However, the published literature remains controversial on whether PD-L1 expression confers prognostic significance independent of immunotherapy in NSCLC. Recent meta-analyses suggest that PD-L1 expression is associated with worse outcomes in NSCLC although other such studies associate PD-L1 expression with favorable prognosis. Moreover, few studies in NSCLC have simultaneously assessed PD-1 expression on tumor-infiltrating leukocytes (TILs), an important contributor to tumor checkpoint status. To assess the prognostic significance of PD-L1/PD-1 status in NSCLC we assembled 280 NSCLC FFPE tissues from lung cancer cases with detailed clinical and questionnaire data available who were recruited from the Metropolitan Detroit region. Tissues were compiled into duplicate tissue-microarrays and were assayed for PD-L1 (223C), PD-1 (NBP1-88104), and whole-transcriptome mRNA expression. PD-L1 staining was assessed by an experienced pathologist and was reported as the percent of tumor cells with membrane positive 223C staining to mirror clinical reporting of PD-L1 status. PD-1 staining was also assessed by the pathologist and was reported as the percent of TILs with membrane positive NBP1-88104 staining. RNA was extracted from FFPE samples and assayed on the Affymetrix Whole-Transcriptome 2.1 array. Array data was batch normalized and Log2 transformed prior to analysis. Immune marker effects on overall survival (OS) were measured with a Cox proportional hazards model, adjusting for tumor stage and histology. 36% of NSCLC tumor samples were PD-L1 positive, defined as ≥ 1% of tumor cells demonstrating positive 223C membrane staining. PD-L1 status was not associated with tumor stage or histology but was strongly correlated with PD-L1 (CD274) mRNA expression (OR=2.37, p=1.1x10-7), adjusting for stage and histology. PD-L1 positive NSCLC were found to have similar OS when compared to tumors with no detectable PD-L1 tumor staining (HR=0.94, p=0.78). Likewise, tumors containing PD-1 positive TILs did not differ in OS when compared to tumors with no detectable PD-1 positive TILs (HR=0.68, p=0.14). Furthermore, there were no detectable differences in OS when combined PD-L1/PD-1 status was assessed (PD-L1+/PD-1+ HR=0.72 p=0.36, PD-L1+/PD-1- HR=1.39 p=0.49, PD-L1-/PD-1+ HR=0.79 p=0.49, PD-L1-/PD-1- Referent). Our findings suggest that neither PD-L1 tumor or PD-1 TIL status are significant prognostic markers in NSCLC independent of immunotherapy.
Citation Format: Donovan Watza, Valerie Murphy, Chrissy Lusk, Angie S. Wenzlaff, Lonardo Fulvio, Christine Neslund-Dudas, Gerold Bepler, Ann G. Schwartz. Immune checkpoint status does not impact overall survival in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2657.