Critical appraisal:Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al 2014

Critical Appraisal

Article being appraised

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014 Nov 13;371(20):1877-88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25265492.

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 progression free survival, overall survival, response rate, response duration and safety of dabrafenib plus trametinib versus dabrafenib alone in patients who had metastatic melanoma with BRAF V600E or V600K mutations

Number of Patients:

423

Total n=423; Two treatment arms: Dabrafenib plus Trametinib (n=211) OR Dabrafenib alone (n=212)

Reported outcome(s):

progression free survival
overall survival
response rate
response duration
safety
pharmakokinetics

Results of outcome(s):

In the intention-to-treat population, the estimated median progression-free survival (the primary end point) was longer in the dabrafenib–trametinib group than in the dabrafenib-only group (9.3 months vs. 8.8 months)

At the time of this report, neither group had reached a median overall survival

The overall response rate as assessed by investigators was 67% (95% CI, 60 to 73) in the dabrafenib– trametinib group versus 51% (95% CI, 45 to 58) in the dabrafenib-only group (P = 0.002)

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

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Risk of bias assessment: randomised controlled trial

Was the trial double-blinded?

I am reasonably certain that the trial was double-blinded (eg identical placebo, active placebo, double-dummy, no revealing side-effects).

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

Included

Completed by

Meghna Kakani

This appraisal has been completed.

Article

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014 Nov 13;371(20):1877-88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25265492.

Assigned to

User:Meghna.kakani

Topic area

Guidelines:Melanoma

Clinical question

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

Form

Form:Critical appraisal

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