Date of Award
Selective Evidence-Based Medicine Review
Master of Science in Health Sciences - Physician Assistant
Physician Assistant Studies
John Cavenagh, MBA, PhD, PA-C
Objective: The objective of this selective EBM review is to determine whether or not combination nivolumab and ipilimumab is safe and effective in patients with melanoma.
Study design: Review of two randomized controlled trials (RCTs) published in 2015, and one cohort study published in 2013.
Data Sources: All of the articles were published in English language, peer reviewed journals and were found using PubMed and Cochrane databases.
Outcomes Measured: The safety of combination nivolumab and ipilimumab was measured by treatment-related grade 3 or 4 adverse effects. The effectiveness was measured by progression-free survival, which is based on disease progression and death.
Results: Wolchok et al. (2013) conducted a cohort study and found that concurrent therapy with nivolumab and ipilimumab had a similar safety profile to previous studies with monotherapy (NNH = 3), and the adverse effects were generally reversible. In a randomized controlled trial, Larkin et al (2015) found that combination nivolumab and ipilimumab was more effective than nivolumab monotherapy in preventing death or disease progression (NNT = -3; p <0.01). Postow et al (2015) conducted a randomized controlled trial that found combination nivolumab and ipilimumab more effective than ipilimumab monotherapy in preventing death or disease progression (NNT = -3; p <0.01).
Conclusions: The cohort study conducted by Wolchok et al showed that nivolumab-plus-ipilimumab had an acceptable safety profile, as its safety was qualitatively similar to monotherapy and the effects were generally reversible. However, it is difficult to conclude that combination nivolumab and ipilimumab is safe in treatment of melanoma based on this one study. The two RCTs demonstrated that combining nivolumab and ipilimumab is effective at preventing death or disease progression of melanoma compared to using nivolumab or ipilimumab alone.
Toscano, Jacob L., "Is Combination Nivolumab And Ipilimumab Safe And Effective In Patients With Melanoma?" (2016). PCOM Physician Assistant Studies Student Scholarship. 412.