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

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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

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

Evidence ratings

Level of evidence

II

Risk of bias
High risk of bias Comments: Please replace this text and include any additional comments in regards to your risk of bias rating

Risk of bias assessment: randomised controlled trial

Was the trial double-blinded?
Outcomes not blinded, substantial side-effects, or not reported.
Was the treatment allocation schedule concealed?
No concealment or unclear (e.g. no approach described, open randomisation lists, person doing recruitment tossing a coin).
Were all randomised participants included in the analysis?
No exclusions or survival analysis used with all subjects included (>95% follow-up for all groups).
The field below is not considered when calculating the risk of bias rating
How was the allocation schedule generated?
Inadequate or not reported
Result of appraisal

Jutta's tick icon.png Included




Completed by

Meghna Kakani


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Article
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.
Assigned to
User:Meghna.kakani
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


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