Epacadostat plus pembrolizumab for advanced melanoma

  • Long GV & al.
  • Lancet Oncol
  • 17 Jun 2019

  • curated by Dawn O'Shea
  • Medical news
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

The addition of the IDO1 selective inhibitor epacadostat to pembrolizumab does not improve survival compared with placebo plus pembrolizumab in patients with unresectable or metastatic melanoma, suggests research published in the Lancet Oncology.

In the international, randomised, placebo-controlled, double-blind, parallel-group, phase 3 trial (ECHO-301/KEYNOTE-252) eligible adults with unresectable stage III or IV melanoma who had not previously been treated with PD-1 or PD-L1 checkpoint inhibitors.

Between 21 June 2016 and 7 Aug 2017, 706 patients were randomly assigned to receive epacadostat plus pembrolizumab (n=354) or placebo plus pembrolizumab (n=352). Median follow-up was 12.4 months (IQR 10.3-14.5).

No significant differences were found between the treatment groups for progression-free survival (median 4.7 months with epacadostat plus pembrolizumab vs 4.9 months with placebo plus pembrolizumab; hazard ratio [HR] 1.00; 95% CI 0.83-1.21; one-sided P=0.52) or overall survival (median not reached in either group; epacadostat plus pembrolizumab vs placebo plus pembrolizumab: HR 1.13; 95% CI 0.86-1.49; one-sided P=0.81).

Because the primary objective of the trial was not met, and because of the strong likelihood that the overall survival comparison would not be significant at the time of the pre-planned final overall survival analysis, the trial was stopped. Follow-up for safety is ongoing.

The authors described the absence of benefit with the combination treatment as “surprising,” given previous non-clinical and early-phase clinical data. In two open-label, phase 1-2 studies of patients with advanced melanoma, epacadostat plus pembrolizumab (ECHO-202)17 and epacadostat plus nivolumab (ECHO-204)18 showed promising antitumour activity, with 56-65% of patients achieving an objective response.