Ipilimumab, an inhibitor of CTLA-4 on T-cells, was the first drug to improve overall survival in patients with advanced melanoma. Subsequently, inhibitors of PD-1, including nivolumab and pembrolizumab, were shown to be superior to ipilimumab with a more favourable safety profile. The combination of ipilimumab and nivolumab is associated with a further improvement in response rate and progression free survival, however the combination is associated with an increased rate of immune related toxicities. In 2015 the FDA approved the combination for the treatment of BRAF wildtype advanced melanoma. This review will examine the preclinical rational for the combination of ipilimumab and nivolumab as well as the efficacy and toxicity data from clinical trials in patients with advanced melanoma. Finally, alternative treatment options are discussed with a focus on patient selection.
- Received March 8, 2016.
- Revision received May 12, 2016.
- Accepted May 14, 2016.
- Copyright ©2016, American Association for Cancer Research.