Ipilimumab in melanoma

Abstract

The treatment of melanoma is evolving rapidly over the past few years. Patients with BRAFv600 mutations can be treated with a combination of a BRAF-inhibitor and an MEK-inhibitor. Patients with BRAF wild-type tumors and BRAFv600 mutated tumors can be treated with immunotherapy i.e. check point inhibitors.

We conducted a comprehensive review of the literature on the efficacy and predictive markers, safety, and pharmacoeconomics of ipilimumab in melanoma

Ipilimumab was the first check point inhibitor reaching the clinic and was approved by  the Food and Drug Administration and the European Medicines Agency  for the treatment of metastatic melanoma in 2011.  More recently, ipilimumab was also approved by FDA in the adjuvant setting for patients with high risk, stage III melanoma. The anti-PD1 directed antibodies pembrolizumab and nivolumab are superior to single agent ipilimumab, which can is no longer be considered the standard first line treatment in metastatic melanoma.

The addition ipilimumab to nivolumab is associated with a higher response rate and a better progressenio-free survival, particularly in patients with PD-L1 negative tumors, albeit at the cost of a steep increase in grade 3-4 adverse event rate. Definitive survival data on this combination are pending and the selection of patients potentially requiring the combination and its pharmacoeconomic implications are to be elucidated.

The optimal sequence (inhibition of BRAF and MEK followed by checkpoint inhibitor or the reverse) in patients with BRAFv600 mutated tumors is unknown.