Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma

作者：Reinhard Dummer, Axel Hauschild, Mario Santinami, Victoria G. Atkinson, Mario Mandalà, John M. Kirkwood, Vanna Chiarion‐Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Mark Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Thierry Lesimple, Ruth Plummer, Kohinoor Dasgupta, Eduard Gasal, Monique Tan, Georgina Venetia Long, Dirk Schadendorf · 发表于：New England Journal of Medicine · 年份：2020 · DOI：10.1056/nejmoa2005493 · 被引用次数：417 · 研究领域：Melanoma and MAPK Pathways、Cutaneous Melanoma Detection and Management、Brain Metastases and Treatment

BACKGROUNDIn the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations.To confirm the stability of the relapse-free survival benefit, longer-term data were needed. METHODSWe randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos.The primary end point was relapse-free survival.Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse.Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached. RESULTSThe minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo).At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61).The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placeb...