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

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

• 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 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

Show/Hide Risk of bias assessment

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

Included

Completed by

Cecilia Taing

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

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

Form

Form:Critical appraisal

Section below only relevant for Cancer Council Project Officer

Edit appraisal assignment