Critical appraisal:Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al 2015

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Critical Appraisal

Article being appraised

Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015 May;16(5):522-30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25840693.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial

Study aims:

To assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence.

Number of Patients:

951

In total, 475 patients were assigned to receive ipilimumab and 476 patients to receive placebo.


Overall, 186 (20%) patients had stage IIIA, 420 (44%) had stage IIIB, and 345 (36%) had stage IIIC disease; 400 (42%) had an ulcerated primary, and 548 (58%) had macroscopic lymph node involvement.
Reported outcome(s):

The primary outcome was recurrence-free survival, and secondary endpoints were distant-metastasis free survival, overall survival, adverse event profile and health-related quality of life.
RFS was defined as the time between the date of randomisation and the date of first recurrence (local, regional or distant metastasis) or death (any cause), which ever occurred first.

Results of outcome(s):

The 3 year recurrence-free survival for the ipilimumab group was 46.5% (95%CI 41.5-51.3) and 34.8% (95%CI 30.1-39.5) for the placebo group, where RFS was significantly longer in the ipilumamb group than in the placebo group (HR, stratifide by stage, 0.75, 95% CI 0.64-0.90; P=0.0013).
The effect of ipilimumab on RFS was consistent across subgroups.

In the ipilimumab group, 465 (99%) of 471 patients had an adverse event of any grade, while 432 (91%) of patients in the placebo group had an adverse event of any grade.

Of 471 patients who started ipilimumab, 245 (52%) discontinued treatment because of an adverse event, and of the 474 patients in the placebo group who received one dose of assigned treatment, 20 (4%) discontinied treatment because of an adverse event.

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias
Low 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?
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)
Result of appraisal

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Completed by

Tamsin Parrish


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Article
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015 May;16(5):522-30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25840693.
Assigned to
User:Tamsin.parrish
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


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