Weighing up the pros and cons of immune checkpoint inhibitors in the treatment of melanoma

The advent of monoclonal antibodies functioning as immune checkpoint inhibitors has changed the way advanced melanoma is treated. CTLA-4 inhibitors such as ipilimumab and the PD-1 inhibitors pembrolizumab and nivolumab all have an established place in the management of metastatic disease. They improve response rates, progression-free and overall survival compared with cytotoxic chemotherapy. In fact, ipilimumab was the first treatment ever to demonstrate an overall survival benefit in advanced melanoma, when compared with the comparator arms of dacarbazine [1] and the vaccine gp100 [2]. As such, even though it can be associated with potentially serious toxicity, the pros clearly outweigh the cons.

More recent studies have established superiority of pembrolizumab and nivolumab over ipilimumab for overall survival, progression-free survival, objective response rate and tolerability [3,4]. The combination of ipilimumab with nivolumab appears particularly potent, with a response rate similar to that of BRAF inhibition (58 vs 57%, respectively) [3,5]. Although overall survival data from the Phase III trial is not yet mature, progression-free survival is significantly greater than ipilimumab (median 11.5 vs 2.9 months; HR 0.42; 99.5% CI: 0.31–0.57; p < 0.001) and numerically greater than nivolumab (median 6.9 months). This is a very promising combination. Responses may be durable and lead to remission, even beyond cessation of therapy for toxicity, a situation that occurs in around a third of those treated [3].

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