Pd-L1 Expression and Overall Survival Among Patients with Melanoma

Abstract

ABSTRACT Aim: Recent clinical trial results suggest programmed cell death ligand-1 (PD-L1) expression may predict response to anti-PD-1 therapy. There are conflicting data regarding PD-L1 expression as a prognostic factor among patients with melanoma treated with standard of care (SOC) therapies. Methods: We evaluated the relationship between PD-L1 expression and overall survival (OS) in 223 melanoma patients diagnosed in Denmark between 2001 and 2010. Tumor PD-L1 expression was measured using a prototype immunohistochemistry assay with the 22C3 antibody, and PD-L1 positivity was defined as staining in ≥1% of cells. Analyses of PD-L1 expression with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test, adjusting for age, gender, stage, and performance status. Results: Median (range) age was 59 years (19-90), and 36% of patients were female. At diagnosis, 48% had stage I-IIIA disease and 45% had stage IIIB-IV disease (6% had missing stage information). 88% of the tumor samples were collected within 6 months of diagnosis. 212 patients received surgery as initial therapy. Among the 167 patients who received chemotherapy or immunotherapy, 17% received 1 regimen, 43% received 2 regimens, and 40% received 3+ regimens. The first-line regimen, excluding adjuvant therapy, was interleukin-2 or interferon (49%), temozolomide (24%), ipilumumab (19%), vemurafenib (3%), or other (5%). 49% of patients were PD-L1 positive. There was no significant association between PD-L1 expression and OS from time of diagnosis, with an adjusted hazard ratio (AHR) of 0.71 for the PD-L1–positive group versus the PD-L1–negative group (95% confidence interval [CI], 0.42-1.21; n = 108) among stage I-IIIA patients, and 1.12 (95% CI, 0.66-1.88; n = 101) among stage IIIB-IV patients. There was also no association between PD-L1 expression and OS among ipilimumab-treated patients (n = 136), with a 1-yr survival rate of 45% (95% CI, 32%-57%) in the PD-L1–positive group and 47% (33%-60%) in the PD-L1–negative group (AHR, 0.93; 95% CI, 0.60-145). Conclusions: Our results do not suggest that PD-L1 is a strong prognostic factor among patients with melanoma treated with SOC therapies, including immunotherapy. Disclosure: T. Steiniche: Corporate-sponsored research–Merck Sharp & Dohme; Z. Wang: Full-time employment–Merck & Co., Inc.; M. Dolled-Filhart: Full-time employment–Merck & Co., Inc.; K. Emancipator: Full-time employment–Merck & Co., Inc.; R. Weiner: Full-time employment–Merck & Co., Inc.; M. Busch-Sorensen: Full-time employment–Merck & Co., Inc.; W. Zhou: Merck Research Laboratories–Full-time employment with stock ownership.; All other authors have declared no conflicts of interest.