Critical appraisal:Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al 2016

Critical Appraisal

Article being appraised

Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016 Sep;17(9):1248-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27480103.

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

Number of Patients:

495

Total N=495 (intent to treat population) . Two treatemtn arms: 1) control arm: 248 placebo + vemurafenib; 2) 247 cobimetinib + vemurafenib

Reported outcome(s):

To compare the survival outcomes of previously untreated patients with histologically confirmed BRAFV600 mutant advanced melanoma that receive either Vemurafenib and placebo, or vemurafenib and cobimeitinib

Results of outcome(s):

Median PFS, months (95% CI) = Placebo and Vemurafenib: 7.2 (5.6-7.5); Cobimetinib and Vemurafenib: 12.3(9.5-13.4)

The median overall survival for patients treated with cobimetinib and vemurafenib was 22·3 months (95% CI 20·3–not estimable) compared with 17·4 months (95% CI 15·0–19·8) for patients treated with vemurafenib (HR 0·70 [95% CI 0·55–0·90], p=0·005; fi gure 4A). 1-year overall survival was 74·5% (95% CI 68·9–80·2) in the cobimetinib and vemurafenib group and 63·8% (57·6–70·0) in the vemurafenib group; 2-year overall survival was 48·3% (41·4–55·2) and 38·0% (31·3–44·7), respectively.

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias

High risk of bias

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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).

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How was the allocation schedule generated?

Adequate (e.g. random number table, computer random generator, coin tossing, card shuffling)

Result of appraisal

Included

Completed by

Meghna Kakani

This appraisal has been completed.

Article

Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 2016 Sep;17(9):1248-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27480103.

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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