2019 ASCO: Long-Term Survival With Dabrafenib Plus Trametinib in Metastatic BRAF-Mutated Melanoma
In an extended analysis of the COMBI-d and COMBI-v trials reported at the 2019 ASCO Annual Meeting (Abstract 9507) and in The New England Journal of Medicine, Robert et al found a 5-year overall survival rate of 34% with the combination of dabrafenib and trametinib in previously untreated metastatic melanoma with a BRAF V600E or V600K mutation.
Study Details
The analysis included 563 patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation randomly assigned to receive the BRAF inhibitor dabrafenib 150 mg twice daily plus the MEK inhibitor trametinib 2 mg once daily in the COMBI-d trial (n = 211) and the COMBI-v trial (n = 352).
Progression-Free and Overall Survival
Median duration of follow-up was 22 months. Progression-free survival was 21% at 4 years and 19% at 5 years. Overall survival was 37% at 4 years and 34% at 5 years. In multivariate analysis, baseline factors associated with improved overall survival included Eastern Cooperative Oncology Group performance status (hazard ratio [HR] = 0.49 for 0 vs 1, P < .001), age (HR = 0.92 per 10-year increment, P = .04), sex (HR = 0.68 for female vs male, P < .001), number of organ sites with metastasis (HR = 0.58 for < 3 vs ≥ 3, P < .001), and lactate dehydrogenase level (HR = 0.47 for normal vs elevated, P < .001); these factors were also associated with prolonged progression-free survival. Complete response occurred in 109 patients (19%) and was associated with 5-year overall survival of 71%.
The investigators concluded,“First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one-third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.”
Disclosure: The study was funded by GlaxoSmithKline and Novartis. For full disclosures of the study authors, visit coi.ascopubs.org or nejm.org.
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