Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma

作者：Caroline Robert, Jean‐Jacques Grob, Daniil Stroyakovskiy, Bogusława Karaszewska, Axel Hauschild, E. Levchenko, Vanna Chiarion‐Sileni, Jacob Schachter, Claus Garbe, Igor Bondarenko, Helen Gogas, Mario Mandalà, John B.A.G. Haanen, Célèste Lebbé, Andrzej Maćkiewicz, Piotr Rutkowski, Paul Nathan, Antoni Ribas, Michael A. Davies, Keith T. Flaherty, Paul Burgess, Monique Tan, Eduard Gasal, Maurizio Voi, Dirk Schadendorf, Georgina V. Long · 发表于：New England Journal of Medicine · 年份：2019 · DOI：10.1056/nejmoa1904059 · 被引用次数：1409 · 研究领域：Melanoma and MAPK Pathways、Cutaneous Melanoma Detection and Management、Fibroblast Growth Factor Research

BACKGROUND: V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors. METHODS: We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively. RESULTS: A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both p...