Programmed Death-Ligand 1 Expression and Response to the Anti–Programmed Death 1 Antibody Pembrolizumab in Melanoma
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Published:2016-12-01
Issue:34
Volume:34
Page:4102-4109
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Daud Adil I.1, Wolchok Jedd D.1, Robert Caroline1, Hwu Wen-Jen1, Weber Jeffrey S.1, Ribas Antoni1, Hodi F. Stephen1, Joshua Anthony M.1, Kefford Richard1, Hersey Peter1, Joseph Richard1, Gangadhar Tara C.1, Dronca Roxana1, Patnaik Amita1, Zarour Hassane1, Roach Charlotte1, Toland Grant1, Lunceford Jared K.1, Li Xiaoyun Nicole1, Emancipator Kenneth1, Dolled-Filhart Marisa1, Kang S. Peter1, Ebbinghaus Scot1, Hamid Omid1
Affiliation:
1. Adil I. Daud, University of California, San Francisco, San Francisco; Antoni Ribas, University of California, Los Angeles; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles; Charlotte Roach and Grant Toland, Dako North America, Carpinteria, CA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Wen-Jen Hwu, The University of Texas MD Anderson Cancer Center, Houston; Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Jeffrey S. Weber, H. Lee...
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.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
506 articles.
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