Date of Award

2012

Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant

Department

Physician Assistant Studies

Department Chair

John Cavanagh, PhD, PA-C

Abstract

Objective: The objective of this selective EBM review is to determine whether or not ipilimumab is an effective treatment in patients diagnosed with metastatic melanoma.

Study Design: Review of three English primary studies published between 2009 and 2010.

Data Sources: Randomized, controlled, double-blind clinical studies comparing ipilimumab +/-gp100 peptide to a placebo +/- gp100. Studies were found using PubMed and Cochrane databases.

Outcomes Measured: Each of the studies measured outcomes of disease progression and overall survival. Response rate to treatment was also measured in two studies. Measurement of these outcomes was achieved utilizing the following classifications systems: [TNM] categorization, & Kaplan-Meier product-limit method of determining survival rates.

Results: In the Hodi et al. study the median overall survival was greater among patients receiving ipilimumab plus glycoprotein100 (gp100), as compared to patients receiving gp100 alone. In the Weber et al. study the median overall response rates were higher for those receiving ipilimumab 10 mg/kg alone, in comparison to ipilimumab 10 mg/kg with budesonide (blind). Subjects with more severe irAEs (immune related adverse events) experienced better disease control compared to those with less serious irAEs. A dose-dependent relationship was illustrated in the Wolchok et al. study; best overall response rate was notably higher for those receiving a higher dose of ipilimumab, opposed to a lower dose.

Conclusion: The results of all three of the reviewed RCT’s and randomized double-blind studies
demonstrated that ipilimumab shows activity in advanced melanoma. According to Hodi et al., ipilimumab may improve overall survival. The study done by Wolchock et al. provides evidence of a dose-dependent relationship on efficacy of ipilimumab, along with irAEs. In terms of safety, it was reported that most adverse events were manageable if not reversible with appropriate treatment, although serious & life-threatening effects were possible. Continued research is needed to determine the optimal dosing and regimen for reducing adverse effects and maximizing efficacy. Further research is desired, particularly at a dose of 10 mg/kg.

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