Ipilimumab plus nivolumab elicits response in patients with rare cancer

Combination treatment with ipilimumab and nivolumab yields meaningful response among patients with multiple refractory rare cancer types, according to a phase II trial.

A team of investigators conducted this prospective, open-label, multicentre phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) in 53 cohorts. They also established a statistical framework to assess each cohort in a two-stage design.

Some 727 eligible patients received treatment, with 24 of the 53 cohorts (45 percent) exhibiting clinical activity, defined as two or more patients with confirmed response.

The median objective response (OR) rate, the primary endpoint, was 12 percent, while the clinical benefit rate was 27 percent. The median progression-free survival (PFS) at 2 years was 10 percent, and the 3-year overall survival (OS) rate was 23 percent. Furthermore, PFS at 6 months showed a modest association with 1- and 3-year OS.

OS was similar between patients who achieved an immune-related OR and those who attained OR. Eighty-two of the 727 enrolled patients (11 percent) had an immune-related PFS of at least 2 years.

Immune-related toxicity rates with the combination therapy were comparable to those seen in previous studies. A total of 102 patients (14 percent) discontinued treatment due to adverse events, the most common of which were fever, diarrhoea, and rash or pruritus.

Notably, patients alive at 6 months who ceased treatment due to immune-related toxicity had longer OS than those who discontinued due to other reasons.

“More robust characterization of biologically defined subsets is underway to optimize therapeutic selection,” the investigators said.