Association of PD-L1 Expression and Response to Pembrolizumab in Advanced Melanoma
In an analysis from the phase IB KEYNOTE-001 trial, Daud et al found that the level of programmed cell death ligand 1 (PD-L1) expression was associated with outcomes of pembrolizumab (Keytruda) treatment in patients with advanced melanoma. These findings were reported in the Journal of Clinical Oncology.
Study Details
In the study, 655 patients received pembrolizumab at 10 mg/kg once every 2 or 3 weeks or 2 mg/kg once every 3 weeks. A total of 451 patients were evaluable for PD-L1 expression.
Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed using a clinical trial immunohistochemistry assay (22C3 antibody); expression was scored using a melanoma scale of 0 to 5 by one of three pathologists blinded to clinical outcome, as follows: 0 = no staining; 1 = 0% to < 1% staining; 2 = 1% to < 10%; 3 = 10% to < 33%; 4 = 33% to < 66%; and 5 = ≥ 66%. A score of ≥ 2 was considered PD-L1–positive.
PD-L1 Score and Outcome
Among the 451 evaluable patients, 344 patients (76%) had PD-L1–positive tumors. Higher melanoma score was associated with a higher objective response rate (P < .001); response rates were 8%, 12%, 22%, 43%, 57%, and 53% for scores of 0, 1, 2, 3, 4, and 5, respectively.
Higher melanoma score was associated with increased progression-free survival (hazard ratio [HR] = 0.76, P < .001) and increased overall survival (HR = 0.76, P < .001). For PD-L1–positive vs –negative patients, median progression-free survival was 5.6 vs 2.8 months (HR = 0.51, P < .001), and median overall survival was 29.9 vs 12.6 months (HR = 0.50, P < .001).
The progression-free survival rate was 39.5% vs 16.3% at 12 months and 29.5% vs 8.9% at 24 months. The overall survival rate was 70.1% vs 50.3% at 12 months and 57.2% vs 32.6% at 24 months.
The investigators concluded: “PD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, [progression-free survival], and [overall survival]; however, patients with PD-L1–negative tumors may also achieve durable responses.”
The study was supported by Merck & Co.
Adil I. Daud, MBBS, of the University of California, San Francisco, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
