Critical appraisal:Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, et al 2017

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Critical Appraisal

Article being appraised

Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017 Apr;18(4):435-445 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28284557.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To compare the efficacy of binimetinib with dacarbazine in patients (either treatment-naïve or received previous immunotherapy) with advanced unresectable or metastatic melanoma harbouring an NRAS mutation.

Number of Patients:

402

Total N=402
269 assigned to Binimeinib part of intention to treat analysis. 133 assigned to the dacarbazine population as part of the intention to treat analysis.
Reported outcome(s):

Progression free survival (PFS)
Overall Survival (OS)
Response Rate (RR)

Results of outcome(s):

Median PFS = 2·8 months (95% CI 2·8–3·6) in binimetinib group; 1·5 months (1·5–1·7) in dacarbazine group (HR 0·62 [95% CI 0·47–0·80]; one-sided p<0·001

Median OS = 11·0 months (95% CI 8·9–13·6) in binimetinib group; 10·1 months (7·0–16·5) in dacarbazine group (HR 1·00 [95% CI 0·75–1·33]; one-sided p=0·50

Median duration of objective response was 11·1 months (95% CI 2·8–not evaluable) in the binimetinib group versus
4·1 months (95% not evaluable) in the dacarbazine group.

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?
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)
Result of appraisal

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Completed by

Meghna Kakani


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Article
Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017 Apr;18(4):435-445 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28284557.
Assigned to
User:Meghna.kakani
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


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