1. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001
- Author
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Hamid, O, Robert, C, Daud, A, Hodi, FS, Hwu, WJ, Kefford, R, Wolchok, JD, Hersey, P, Joseph, R, Weber, JS, Dronca, R, Mitchell, TC, Patnaik, A, Zarour, HM, Joshua, AM, Zhao, Q, Jensen, E, Ahsan, S, Ibrahim, N, and Ribas, A
- Subjects
Vaccine Related ,Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Immunological ,Drug Administration Schedule ,Follow-Up Studies ,Humans ,Kaplan-Meier Estimate ,Melanoma ,Response Evaluation Criteria in Solid Tumors ,Skin Neoplasms ,pembrolizumab ,melanoma ,treatment-naive ,long-term follow-up ,metastatic ,overall survival ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundPembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.Patients and methodsPatients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017).ResultsKEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE.ConclusionsThis 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma.Clinical trial registryClinicalTrials.gov, NCT01295827.
- Published
- 2019