Critical appraisal:Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al 2015

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Critical Appraisal

Article being appraised

Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015 Jan 1;372(1):30-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25399551.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To compare the overall survival, progression free survival, objective response rate, safety and efficacy in patients with metastatic melanoma with a BRAFV600 mutation who are treated with either a combination of dabrafenib and trametinib OR vemruafenib orally as first-line therapy.

Number of Patients:

704

Total n=704. Two treatment arms: 1) Combination therapy of dabrafenib and trametinib (n=352); 2) Vemurafenib monotherapy (n=352). These numbers represent the intent to treat population.
Reported outcome(s):

Median Overall Survival
Rate of Overall Survival
Median Progression Free Survival
Hazard ratio for PFS
Objective Response Rate (RECIST version 1.1)
Median duration of response

Results of outcome(s):

Median Overall Survival
Vemurafenib Monotherapy: 17.2 months
Combination Therapy: not reached

Median Progression Free Survival
Vemurafenib Monotherapy: 7.3 months
Combination Therapy: 11.4 months

Objective Response Rate (RECIST version 1.1):
Vemurafenib Monotherapy: 51% (95% CI, 46 to 57)
Combination Therapy: 64% (95% CI, 59 to 69)

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?
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


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


Article
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015 Jan 1;372(1):30-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25399551.
Assigned to
User:Meghna.kakani
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


Section below only relevant for Cancer Council Project Officer

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