Pembrolizumab Provides Durable Activity in Mucosal Melanoma

Pembrolizumab demonstrated durable activity in 3 clinical trials in previously treated patients with mucosal melanoma.

Marcus Butler, MD

Pembrolizumab (Keytruda) demonstrated durable activity in 3 clinical trials in previously treated patients with a rare subtype of melanoma, according to a presentation during the 2017 European Cancer Congress in Amsterdam.

Among the patients with advanced melanoma treated with pembrolizumab in the KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006 studies, patients with mucosal melanoma (n = 84) showed a median duration of response of 27.6 months.

“The data presented here are important because they prove that patients with mucosal melanoma can benefit from anti—PD-1 therapy and should not be excluded from this treatment,” said investigator Marcus Butler, MD, in a statement. “At this stage we don’t know why some mucosal melanoma patients responded to pembrolizumab, while others did not. This is an important question and research is ongoing.”

Across the 3 KEYNOTE trials, 84 of 1567 patients (5%) had mucosal melanoma. Of these 84 patients, 57% were women, 49% were at least 65 years old, and 32% had an ECOG performance status of 1. Eight percent of the patients hadBRAFV600 mutations, 81% had M1c disease, and of the patients with known PD-L1 status, 70% had PD-L1—positive tumors.

All of the patients were previously treated, with 90% having received at least 1 prior therapy, and 8% had received more than 3. Ipilimumab (Yervoy) was previously taken by 39% of patients.

In the 3 KEYNOTE trials, patients received the PD-1 inhibitor at 3 different dosages, 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks.

The objective response rate (ORR) in the patients with mucosal melanoma was 19% (95% CI, 12-29) with 16 patients responding, and the disease control rate (DCR) was 31% (95% CI, 22-42). The median progression-free survival (PFS) rate was 2.8 months (95% CI, 2.7-2.8) and the median overall survival (OS) rate was 11.3 months (95% CI, 7.7-16.6).

“Sixteen of these patients (19%) responded to treatment with pembrolizumab, of whom 12 are still alive without their disease progressing and, so far, the longest time some of these patients have continued to be successfully treated is more than 27 months,” said Butler, of the Cancer Clinical Research Unit of the Princess Margaret Cancer Centre.

Of the patients previously treated with ipilimumab, the ORR was 15% (95% CI, 7-31) with 5 patients responding and the DCR was 27% (95% CI, 15-44). “Our results show that patients benefited from pembrolizumab regardless of whether or not they had been pre-treated with ipilimumab,” said Butler.

In the 3 trials, patients with nonmucosal melanoma had an ORR of 33% (95% CI, 30-35) and the DCR was 47% (95% CI, 44-49). The median PFS was 4.2 months (95% CI, 3.6-5.5) and the median OS was 23.5 months (95% CI, 21.1-26.8).

“Immunotherapy for melanoma has revolutionized treatment of the disease. There are some patients with mucosal melanoma who have had complete responses to pembrolizumab and essentially return to a normal life. Some, of course, have less spectacular responses, but they still benefit from therapy,” said Butler. “In earlier studies, mucosal melanoma was excluded since it is a rare subtype. These findings suggest that mucosal melanoma patients should be offered immunotherapy as standard of care and not excluded. Response rates may be a bit lower than for other types of melanoma, so further studies to improve benefit need to be conducted.”

“For rare cancer types, it is difficult to evaluate new treatments in normal sized trials. But here, Butler and colleagues pull three trials together and show that long-lasting responses also occur with pembrolizumab in patients with mucosal melanoma,” Peter Naredi, chair of the European Cancer Congress and president of the European Cancer Organization, said in a statement.


Butler M, Hamid O, Ribas A, et al. Efficacy of pembrolizumab in patients with advanced mucosal melanoma enrolled in the KEYNOTE-001, 002, and 006 studies. Presented at: 2017 European Cancer Congress; January 27-30, 2017; Amsterdam, The Netherlands. Abstract 1142.