Critical appraisal:Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al 2014

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Critical Appraisal

Article being appraised

Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014 Nov 13;371(20):1867-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25265494.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To compare investigator-assessted progression free survival between the combination treatment: Vemurafenib and Cobimetinib and Vemurafenib alone (with placebo)

Number of Patients:

495

Two treatment arms: Combination treatment of Vemurafenib and Cobimetinib (n=247) and Vemrafeib with Placebo (n=248).
Reported outcome(s):

Progression Free survival
Best Response - no % (Complete response, partial response, stable disease, progressive disease etc.)
Median duration of response
Overall survival at 9 months
Overall survival (median duration, hazard ratio for death, P value)

Results of outcome(s):

Median PFS==> Vemurafenib + placebo: 6.2 (95%, 5.6-7.4); Vemurafenib + Cobimetinib: 9.9 (95%, 9.0 - NR)
Median OS==> not reached for either groups.
Objective Response Rate ==> Vemurafenib + placebo: 45%; Vemurafenib + Cobimetinib:68% (p<0.001)

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

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Completed by

Meghna Kakani


Jutta's tick icon.png This appraisal has been completed.


Article
Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014 Nov 13;371(20):1867-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25265494.
Assigned to
User:Meghna.kakani
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


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