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.