Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma

Caroline Robert, Antoni Ribas, Omid Hamid, Adil Daud, Jedd D. Wolchok, Anthony M. Joshua, Wen Jen Hwu, Jeffrey S. Weber, Tara C. Gangadhar, Richard W. Joseph, Roxana Dronca, Amita Patnaik, Hassane Zarour, Richard Kefford, Peter Hersey, Jin Zhang, James Anderson, Scott J. Diede, Scot Ebbinghaus, F. Stephen Hodi

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    356 Citations (Scopus)

    Résumé

    Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study (ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for $ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of $ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

    langue originaleAnglais
    Pages (de - à)1668-1674
    Nombre de pages7
    journalJournal of Clinical Oncology
    Volume36
    Numéro de publication17
    Les DOIs
    étatPublié - 10 juin 2018

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