Critical appraisal:Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al 2015

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Critical Appraisal

Article being appraised

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 2015 Aug 1;386(9992):444-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26037941.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To assess overall survival following dabrafenib plus trametinib v dabrafenib plus placebo.

Number of Patients:

423

unresectable stage IIIC and IV metastatic melanoma

randomised: 423
- dabrafenib plus trametinib: 211
- dabrafenib plus placebo: 212

intention to treat population
Reported outcome(s):

OS, PFS

Results of outcome(s):

OS: 25.1 mo 95CI 19.2-not reached v 18.7 mo 95CI 15.2-23.7, p=0.01; dabrafenib+trametinib v dabrafenib+placebo
1-y survival and 2-y survival were both greater in the dabrafenib+trametinib group than in dabrafenib+placebo
Median PFS: 11.0 v 8.8, p=0.0004; dabrafenib+trametinib v dabrafenib+placebo
overall response: 69% v 53%, p=0.0014; dabrafenib+trametinib v dabrafenib+placebo

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias
Low risk of bias Comments: double-blinded, treatment allocation described, intention to treat population

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?
Adequately concealed (e.g. central randomisation, numbered or coded bottles, drugs prepared by pharmacy).
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?
Adequate (e.g. random number table, computer random generator, coin tossing, card shuffling)
Size of effect
1 Reason for decision: Please replace this text and briefly describe the reasons for your rating
Relevance of evidence
1 Additional comments: survival outcomes
Result of appraisal

Jutta's tick icon.png Included




Completed by

Cecilia Taing


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


Article
Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 2015 Aug 1;386(9992):444-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26037941.
Assigned to
User:Cecilia.taing
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


Section below only relevant for Cancer Council Project Officer

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