Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma Journal Article


Authors: Daud, A. I.; Wolchok, J. D.; Robert, C.; Hwu, W. J.; Weber, J. S.; Ribas, A.; Hodi, F. S.; Joshua, A. M.; Kefford, R.; Hersey, P.; Joseph, R.; Gangadhar, T. C.; Dronca, R.; Patnaik, A.; Zarour, H.; Roach, C.; Toland, G.; Lunceford, J. K.; Li, X. N.; Emancipator, K.; Dolled-Filhart, M.; Kang, S. P.; Ebbinghaus, S.; Hamid, O.
Article Title: Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma
Abstract: Purpose: Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods: Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score ≥ 2 (membranous staining in ≥ 1% of cells) was considered positive. Results: Of 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1-positive tumors. Demographic and staging variables were equally distributed among PD-L1-positive and -negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed (P < .001 for each). Objective response rate was 8%, 12%, 22%, 43%, 57%, and 53% for MEL 0, 1, 2, 3, 4, and 5, respectively. Conclusion: PD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, PFS, and OS; however, patients with PD-L1-negative tumors may also achieve durable responses. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 34
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-12-01
Start Page: 4102
End Page: 4109
Language: English
DOI: 10.1200/jco.2016.67.2477
PROVIDER: scopus
PUBMED: 27863197
PMCID: PMC5562434
DOI/URL:
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
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  1. Jedd D Wolchok
    756 Wolchok