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

Adil I. Daud, Jedd D. Wolchok, Caroline Robert, Wen Jen Hwu, Jeffrey S. Weber, Antoni Ribas, F. Stephen Hodi, Anthony M. Joshua, Richard Kefford, Peter Hersey, Richard Joseph, Tara C. Gangadhar, Roxana Dronca, Amita Patnaik, Hassane Zarour, Charlotte Roach, Grant Toland, Jared K. Lunceford, Xiaoyun Nicole Li, Kenneth EmancipatorMarisa Dolled-Filhart, S. Peter Kang, Scot Ebbinghaus, Omid Hamid

Research output: Contribution to journalArticle

243 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4102-4109
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number34
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., ... Hamid, O. (2016). Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. Journal of Clinical Oncology, 34(34), 4102-4109. https://doi.org/10.1200/JCO.2016.67.2477