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瑞士苏黎世大学医院Reinhard Dummer团队对达拉非尼联合曲美替尼治疗III期黑色素瘤进行了5年分析。2020年9月2日,该研究发表在《新英格兰医学杂志》上。

在先前报道的3期临床试验的初步分析中,达拉非尼+曲美替尼辅助治疗BRAF V600E或V600K突变的III期黑色素瘤切除患者12个月,无复发生存期比安慰剂更长。为了确认无复发生存获益的稳定性,仍需长期数据。

研究组招募了870例BRAF V600E或V600K突变的III期黑色素瘤切除患者,分别接受口服达拉非尼+曲美替尼或安慰剂治疗,为期12个月。主要终点是无复发生存期。


研究结果表明,达拉非尼+曲美替尼治疗BRAF V600E或V600K突变的III期黑色素瘤患者,无复发或远端转移的生存期更长,且无明显毒副作用。


Author: Reinhard Dummer, M.D.,, Axel Hauschild, M.D.,, Mario Santinami, M.D.,, Victoria Atkinson, M.D.,, Mario Mandalà, M.D.,, John M. Kirkwood, M.D.,, Vanna Chiarion Sileni, M.D.,, James Larkin, M.D., Ph.D.,, Marta Nyakas, M.D.,, Caroline Dutriaux, M.D.,, Andrew Haydon, M.B., B.S., Ph.D.,, Caroline Robert, M.D., Ph.D.,, Laurent Mortier, M.D., Ph.D.,, Jacob Schachter, M.D.,, Thierry Lesimple, M.D.,, Ruth Plummer, M.D.,, Kohinoor Dasgupta, Ph.D.,, Eduard Gasal, M.D.,, Monique Tan, M.D.,, Georgina V. Long, M.B., B.S., Ph.D.,, and Dirk Schadendorf, M.D.

Issue&Volume: 2020-09-02



In 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.


We 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.


The 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 placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period.


In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects.

DOI: 10.1056/NEJMoa2005493

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2005493