Keytruda Benefits Rare Melanoma Subtype in Three Trials

Previously treated patients with a rare subtype of melanoma had durable activity on Keytruda (pembrolizumab), according to data from three clinical trials presented at the 2017 European Cancer Congress in Amsterdam.

Patients with mucosal melanoma (84 patients) treated with Keytruda in the KEYNOTE-001, KEYNOTE-002 and KEYNOTE-006 studies demonstrated a median duration of response of 27.6 months.

These data are particularly important because they show that patients with this rare subtype of melanoma can benefit from anti—PD-1 therapy, said investigator Marcus Butler, M.D., 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,” Butler, of the Cancer Clinical Research Unit of the Princess Margaret Cancer Centre, explained.

In the three KEYNOTE trials, 84 of 1,567 patients (5 percent) had mucosal melanoma. Of these 84 patients, 57 percent were women, 49 percent were at least 65 years old, and 32 percent had an ECOG performance status of 1. Eight percent of the patients had BRAF V600 mutations, 81 percent had M1c disease, and of the patients with known PD-L1 status, 70 percent had PD-L1—positive tumors.

All of the patients were previously treated; 90 percent of patients had received at least one prior therapy, and 8 percent had received more than three therapies. Thirty-nine percent of patients had previously been treated with Yervoy (ipilimumab).

Across the three KEYNOTE trials, patients received Keytruda at three different doses: 2 mg/kg every three weeks, 10 mg/kg every three weeks, or 10 mg/kg every two weeks.

The objective response rate (ORR) in the patients with mucosal melanoma was 19 percent with 16 patients responding, and the disease control rate (DCR) was 31 percent. The median progression-free survival (PFS) rate was 2.8 months and the median overall survival (OS) rate was 11.3 months.

“Sixteen of these patients (19 percent) 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 patients previously treated with Yervoy, the ORR was 15 percent with five patients responding and the DCR was 27 percent. “Our results show that patients benefited from Keytruda regardless of whether or not they had been pre-treated with ipilimumab,” said Butler. In the three trials, patients with nonmucosal melanoma had an ORR of 33 percent and the DCR was 47 percent. The median PFS was 4.2 months and the median OS was 23.5 months.

In his presentation, Butler emphasized the impact that immunotherapy has had thus far on the treatment landscape of melanoma.

“Immunotherapy for melanoma has revolutionized treatment of the disease. There are some patients with mucosal melanoma who have had complete responses to Keytruda and essentially return to a normal life. Some, of course, have less spectacular responses, but they still benefit from therapy,” said Butler.

He added that earlier studies have previously excluded patients with mucosal melanoma, as it is a rare subtype of the disease.

“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,” he said.

“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.