Critical appraisal:Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al 2012

Critical Appraisal

Article being appraised

Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012 Jul 12;367(2):107-14 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22663011.

Applicable clinical question

Does systemic drug therapy improve progression-free, overall survival in unresectable stage III and stage IV melanoma?

Key Facts

Study Design

randomised controlled trial

Study aims:

To compare trametinib (2 mg orally) treatment with chemotherapy (dacarbazine or paclitaxel) treatment in patients with metastatic melanoma with a V600E or V600K BRAF mutation

Number of Patients:

322

Two treatment groups: Trametinib (n=214) with chemotherapy via dacarbazine or paclitaxel (n=108). Note that patients in the chemotherapy group who had disease prgoression were permitted to corss over to receive trametinib (51 of the 108 patients did cross over)

Reported outcome(s):

Progression Free Survival
Overall Survival
Response Rate

Results of outcome(s):

In the intention-to-treat population, the median duration of progression-free survival was 4.8 months in the trametinib group as compared with 1.5 months in the chemotherapy group (hazard ratio for progression, 0.45; 95% confidence interval [CI], 0.33 to 0.63; P<0.001)

Median overall survival had not been reached at the time of this report, and follow-up continues in these cohorts.

In the intention-to-treat analyses, the response rate, which was defined as the percentage of patients with a confirmed complete or partial response as assessed according to RECIST by the site investigators, was 22% (95% CI, 17 to 28) in the trametinib group and 8% (95% CI, 4 to 15) in the chemotherapy group (P=0.01)

Includes an economic evaluation

no