Abstract 114P
Background
In KEYNOTE-427 (a single arm Phase 2 trial of pembrolizumab monotherapy in advanced renal cell carcinoma [aRCC] patients) there was an association of programmed death ligand 1 (PD-L1) expression, using combined positive score (CPS), and tumor response. There are limited data on the association of PD-L1 expression using CPS and outcomes in patients treated with non-immunotherapy (IO) based regimens.
Methods
PD-L1 expression and association with outcomes was evaluated in 255 advanced clear-cell RCC (ccRCC) patients treated with standard of care at Aarhus University Hospital between 2006 and 2016. PD-L1 expression was measured by immunohistochemistry in nephrectomy specimens with PD-L1+ defined as a CPS ≥1. PD-L1 association was evaluated with best overall response (% complete or partial response) defined by clinician assessment, and progression-free and overall survival (PFS, OS) calculated using time to event analyses. Multivariate modeling was used, adjusted for International mRCC Database Consortium (IMDC) score, age, and other covariates.
Results
Among the 255 aRCC patients, the majority received VEGF inhibitors (mainly sunitinib [44%], pazopanib [38%]), median age was 63 (range: 37-88) years, with 68% male, 45%/34% IMDC int./poor risk, 24% sarcomatoid differentiation, and 69% Fuhrman grade III/IV. Best overall response rate was 26% with median PFS of 11 months. Overall, 61% of patients were PD-L1+, with a significant association (p<0.05) of PD-L1 expression with increasing Fuhrman grade, sarcomatoid differentiation, necrosis, and increasing IMDC risk. There was no association of PD-L1 expression with response rate or PFS. A negative association (p=0.04) was observed with OS, with shorter median survival for PD-L1+ (14.5 months [95%CI 10.2, 18.3]) compared with PD-L1 (28.3 months [95%CI 20.5,35.2]) When excluding patients receiving IO therapy (6%), response and PFS did not change, but OS association was borderline significant after multivariate adjustment (p=0.1).
Conclusions
PD-L1 expression may be a negative prognostic factor among aRCC patients. There was no correlation of PD-L1 expression levels with response to VEGF inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
F. Donskov: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Ipsen. C.A. Pinto: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. R. Predoui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. F. Kong: Full/Part-time employment: Merck & Co., Inc. C. Fox: Full/Part-time employment: Merck & Co., Inc. K. Skaarup: Full/Part-time employment: MSD. R. Perini: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. T. Steiniche: Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.