This article is more than 5 years old. Information may no longer be current.
Pembrolizumab active against advanced mucosal melanoma
Click Here to Manage Email Alerts
Pembrolizumab demonstrated durable activity in patients with advanced mucosal melanoma regardless of previous treatment with ipilimumab, according to data from KEYNOTE clinical trials presented at the European Cancer Congress.
“These findings suggest that mucosal melanoma patients should be offered immunotherapy as standard of care and not excluded,” Marcus Butler, MD, oncologist at Princess Margaret Cancer Center in Toronto, Canada, said in a press release.
The KEYNOTE-001, 002 and 006 studies included 1,567 patients with advanced melanoma treated with pembrolizumab (Keytruda, Merck) in doses of 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks.
Pembrolizumab previously demonstrated safety and efficacy for the treatment of advanced melanoma in these trials. Pembrolizumab — which binds to PD-1 and blocks its interaction between PD-L1 and PD-L2 — activates lymphocyte cells that can affect tumor cells and healthy cells, according to the release. Previously, patients with mucosal melanoma — a subtype of melanoma — had been excluded from immunotherapy treatments due to the rarity of the disease.
The KEYNOTE trials included 84 (5%) patients with mucosal melanoma (57% women; 49% aged 65 years or older).
Fifty-eight percent of these patients had a baseline tumor size larger than 77.7 mm and 32% had an ECOG performance status of 1. Seventy percent of patients with known PD-L1 status had PD-L1–positive tumors.
Ninety percent of patients were previously treated with more than one therapy, including 8% who had received three or more prior therapies; 39% were previously treated with ipilimumab (Yervoy, Bristol-Myers Squibb).
The overall response rate in patients with mucosal melanoma was 19% (95% CI, 12-29) and the disease control rate was 31% (95% CI, 22-42). The median time to response among 16 responding patients was 12.4 weeks (range, 11.1-84.1). Twelve patients were alive without any signs of progression, and the median duration of response was 27.6 months (range, 1.1+ to 27.6).
Median PFS was 2.8 months (95% CI, 2.7-2.8) and median OS was 11.3 months (95% CI, 7.7-16.6).
“Immunotherapy for melanoma has revolutionized treatment of the disease,” Butler said. “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.”
In patients with mucosal melanoma pretreated with ipilimumab, the ORR was 15% (95% CI, 7-31), the disease control rate was 27% (95% CI, 15-44) and 80% of responders (n = 4 of 5) were alive without signs of progression. The median duration of response was 27.6 months.
In the nonmucosal melanoma population treated with at least one dose of pembrolizumab (n = 1,483) the ORR was 33% (95% CI, 30-35), the disease control rate was 47% (95% CI, 44-49) and 72% were still alive without signs of progression. The median OS was almost 2 years (23.5 months; 95% CI, 21.1-26.8) and median PFS was 4.2 months (95% CI, 3.6-5.5).
“Response rates may be a bit lower than for other types of melanoma, so further studies to improve benefit need to be conducted,” Butler said. – by Melinda Stevens
Reference:
Butler M, et al. Abstract 1142. Presented at: European Cancer Congress; January 27-30; Amsterdam.
Disclosures: The study was funded by Merck. Butler reports advisory board roles with Bristol-Myers Squibb, Merck and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
Back to Top
Sanjiv S. Agarwala, MD
Major advances have been made in the treatment of cutaneous melanoma in the last several years. Immunotherapy with the checkpoint inhibitors pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, Bristol-Myers Squibb) have transformed the survival of advanced melanoma and have become a standard of care. Data with combination therapy with the anti–CTLA-4 antibody ipilimumab (Yervoy, Bristol-Myers Squibb) combined with nivolumab appear even more impressive, with response rates of over 50%, albeit with greater toxicity.Melanoma is not one disease. There are distinct biological variants, such as mucosal, acral lentiginous and uveal melanomas. Data obtained in trials that predominantly enroll patients with cutaneous melanoma cannot always be extrapolated to these variants. For example, mucosal melanomas rarely harbor the BRAF mutation, have a higher incidence of c-KIT mutations and present with greater frequency in non-Caucasian populations, such as in China. Improving response rates and survival in this population of patients has been a difficult proposition.
The results of the study by Butler and colleagues, although encouraging, are lower than that seen in the much larger group of patients with cutaneous melanomas. They are, however, superior to an earlier report from Italian investigators who reported a response rate of 12% and median survival of 6.4 months with ipilimumab. There have also been reports of targeted therapies, particularly with imatinib, with a suggestion of responses that may occur in patients harboring variants of the c-KIT mutation. But, responses have been infrequent, and this therapy is not approved nor widely used for mucosal melanomas. Reports of binimetinib (MEK162, Array BioPharma) in melanoma harboring nRAS mutations have been encouraging, but this mutation occurs rarely in mucosal melanomas. Of note, randomized trial data in this disease are lacking, which makes drawing firm conclusions challenging.
It is apparent that successful therapy for patients with metastatic mucosal melanomas remains an unmet need, and additional trials are necessary. For the time being, immunotherapy with agents such as pembrolizumab is certainly a viable and appropriate treatment choice, given the relatively high response rates and manageable toxicity.
References:
Del Vecchio M, et al. Eur J Cancer. 2013;doi:10.1016/j.ejca.2013.09.007.
Dummer R, et al. Abstract 9500. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Click Here to Manage Email Alerts