Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1-positive nasopharyngeal carcinoma: Results of the KEYNOTE-028 study

Chiun Hsu, Se Hoon Lee, Samuel Ejadi, Caroline Even, Roger B. Cohen, Christophe Le Tourneau, Janice M. Mehnert, Alain Algazi, Emilie M.J. Van Brummelen, Sanatan Saraf, Pradeep Thanigaimani, Jonathan D. Cheng, Aaron R. Hansen

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    370 Citations (Scopus)

    Résumé

    Purpose: To establish the safety profile and antitumor activity of the anti-programmed death 1 receptor monoclonal antibody, pembrolizumab, in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that expressed programmed death-ligand 1 (PD-L1). Patients and Methods: KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors. Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes. Patients received pembrolizumab 10 mg/kg every 2 weeks up to 2 years or until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR) per investigator review. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) every 8 weeks for the first 6 months and every 12 weeks thereafter. Results: Twenty-seven patients received pembrolizumab. Median age was 52.0 years (range, 18 to 68 years); 92.6% received prior therapies for RM-NPC; 70.4% had received three or more therapies. Partial response and stable disease were observed in seven and 14 patients, respectively, for an ORR of 25.9% (95% CI, 11.1 to 46.3) overamedian follow-up of 20 months. ORR by central review was similar (26.3%). Drug-related adverse events that occurred in 15% or more of patients included rash (25.9%), pruritus (25.9%), pain (22.2%), hypothyroidism (18.5%), and fatigue (18.5%). Grade $ 3 drug-related adverse events occurred in eight patients (29.6%), and there was one drug-related death (sepsis). As of the data cutoff (June 20, 2016), two patients remained on pembrolizumab treatment. Conclusion: Pembrolizumab demonstrated antitumor activity and a manageable safety profile in patients with RM-NPC.

    langue originaleAnglais
    Pages (de - à)4050-4056
    Nombre de pages7
    journalJournal of Clinical Oncology
    Volume35
    Numéro de publication36
    Les DOIs
    étatPublié - 20 déc. 2017

    Contient cette citation