Critical appraisal:Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al 2016

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Critical Appraisal

Article being appraised

Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med 2016 Nov 10;375(19):1845-1855 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27717298.


Applicable clinical question

Key Facts

Study Design

randomised controlled trial - Cochrane tool

Study aims:

To report on the efficacy of adjuvant therapy with ipilimumab on all survival endpoints in patients with high-risk stage III melanoma after complete lymph-node dissection.

Number of Patients:

951

475 patients were randomly assigned to receive ipilimumab and 476 to receive placebo. Six patients (4 int he ipilumumab group and 2 in the placebo group) did not start the randomly assigned regimen.
Reported outcome(s):

The primary endpoint was recurrence free survival, and the secondary end points included overall survival, distant metastasis-free survival, safety and health-related quality of life.

Overall survival was defined as the time from randomisation until death from any cause. Distant metastasis-free survival was defined as the time from randomisation until the date of the first distant metastasis or death from any cause.

Results of outcome(s):

The overall survival rate at 5 years was 65.4% (95% CI, 60.8-69.9) in the ipilimumab group, compared to 54.4% (95% CI, 497-58.9) in the placebo group. Overall survival was significantly longer in the ipilimumab group (HR for death from any cause, 0.72; 95% CI, 0.58-0.88; P-0.001); risk of death 28% lower with ipilimumab than with placebo.

The rate of distant metastasis free survival at 5 years was higher in the ipilimumab group than in the placebo group (48.3% vs 38.9%; HR for distant metastasis or death, 0.76; 95.8% CI, 0.64-0.92; P-0.002).

Of the 471 patients who started ipilumumab, 251 (53.3%) discontinued treatment owing to an adverse event, and 22/474 (4.6%) patients who received placebo discontinued treatment owing to an adverse event.
A total of 63 patients (13.4%) in the ipilumumab group and 143 (30.2%) of patients in the placebo group completed the 3 year treatment period.

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias
Unclear 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 (Cochrane risk of bias tool)

Random sequence generation
Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.Jutta's question mark icon.png
Minimisation technique
What was the risk of bias from the random sequence generation?Jutta's question mark icon.png
Low
Allocation concealment
Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of or during, enrolment.Jutta's question mark icon.png
No response
What was the risk of bias from the allocation concealment?Jutta's question mark icon.png
Unclear
Blinding
Describe all measures used, if any, to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.Jutta's question mark icon.png
Double blind
What was the risk of bias from the blinding of participants and personnel and outcome assessors?Jutta's question mark icon.png
Low
Incomplete outcome data
Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.Jutta's question mark icon.png
No response
What was the risk of bias from incomplete outcome data?Jutta's question mark icon.png
Low
Selective outcome reporting
State how the possibility of selective outcome reporting was examined by the review authors and what was found.Jutta's question mark icon.png
No response
What was the risk of bias from selective outcome reporting? Assessments should be made for each main outcome (or class of outcomes).Jutta's question mark icon.png
Low
Other sources of bias
Describe any other sources of biasJutta's question mark icon.png
No response
What was the risk of bias from other sources?Jutta's question mark icon.png
Unclear
Result of appraisal

Jutta's tick icon.png Included




Completed by

Tamsin Parrish


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


Article
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med 2016 Nov 10;375(19):1845-1855 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27717298.
Assigned to
User:Tamsin.parrish
Topic area
Guidelines:Melanoma
Clinical question
Form
Form:Critical appraisal


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