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Pembrolizumab Demonstrates Durable Responses in Rare Subtype of Melanoma

Lisa Miller
Published: Tuesday, Jan 31, 2017

Marcus Butler, MD

Marcus Butler, MD

Pembrolizumab (Keytruda) provided durable activity for previously treated patients with a rare subtype of melanoma, according to data coming out of 3 clinical trials, which were presented during the 2017 European Cancer Congress in Amsterdam.

Patients with mucosal melanoma (n = 84) treated with pembrolizumab 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, 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,” Butler, of the Cancer Clinical Research Unit of the Princess Margaret Cancer Centre, explained.

In 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 had BRAF V600 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; 90% of patients had received at least 1 prior therapy, and 8% had received more than 3 therapies. Thirty-nine percent of patients had previously been treated with ipilimumab (Yervoy).

Across the 3 KEYNOTE trials, patients received pembrolizumab at 3 different doses: 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 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).

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 pembrolizumab 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.
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.



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TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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