- Title
- Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma
- Creator
- 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
- Relation
- Journal of Clinical Oncology Vol. 34, Issue 34, p. 4102-4109
- Publisher Link
- http://dx.doi.org/10.1200/JCO.2016.67.2477
- Publisher
- American Society of Clinical Oncology
- Resource Type
- journal article
- Date
- 2016
- Description
- 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.
- Subject
- programmed death-ligand 1 (PD-L1); anti–programmed death 1 (PD-1); melanoma; pembrolizumab
- Identifier
- http://hdl.handle.net/1959.13/1344419
- Identifier
- uon:29414
- Identifier
- ISSN:0732-183X
- Language
- eng
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