Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma
In: Journal of Clinical Oncology Vol. 34, Issue 34, 2016, S. 4102-4109
Online
academicJournal
Zugriff:
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.
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Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma
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Autor/in / Beteiligte Person: | Daud, Adil I ; Wolchok, Jedd D. ; Joseph, Richard ; Gangadhar, Tara C. ; Dronca, Roxana ; Patnaik, Amita ; Zarour, Hassane ; Roach, Charlotte ; Toland, Grant ; Lunceford, Jared K. ; Li, Xiaoyun Nicole ; Emancipator, Kenneth ; Robert, Caroline ; Dolled-Filhart, Marisa ; Kang, S. Peter ; Ebbinghaus, Scot ; Hamid, Omid ; Hwu, Wen-Jen ; Weber, Jeffrey S. ; Ribas, Antoni ; Hodi, F. Stephen ; Joshua, Anthony M. ; Kefford, Richard ; Hersey, Peter ; The University of Newcastle. Faculty of Health & Medicine, School of Medicine and Public Health |
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Zeitschrift: | Journal of Clinical Oncology Vol. 34, Issue 34, 2016, S. 4102-4109 |
Veröffentlichung: | American Society of Clinical Oncology, 2016 |
Medientyp: | academicJournal |
ISSN: | 0732-183X (print) |
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