Pembrolizumab Active Against Rare Melanoma, Extends Survival in Bladder Cancer
In addition to being effective against types of melanoma, pembrolizumab may extends survival in patients with bladder cancer.
Clinical trials with pembrolizumab demonstrated that the recently FDA-approved immunotherapy is active against mucosal melanoma and extends survival in patients with bladder cancer. Results from 2 clinical trials were presented at the 2017 European Cancer Congress.1,2
Mucosal melanoma, a rare subtype of melanoma, occurs in the mucosal linings of body cavities. Its cause is unknown. Approximately 1% of melanoma cases are mucosal. Prognosis is typically poor due to the usually late diagnosis.
"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 Marcus Butler, MD, a medical oncologist at the Princess Margaret Cancer Center, Toronto, Canada.
In the remaining 1483 KEYNOTE patients with other forms of advanced melanoma, among those who received at least 1 dose of pembrolizumab, 33% responded to treatment, 72% were alive with no progressed disease, and median overall survival (OS) was almost 2 years. Median OS in mucosal melanoma was 11.3 months.
Pembrolizumab inhibits programmed cell death protein 1 (PD-1), a T cell surface receptor. PD-L1 is one of its ligands and is overexpressed on cell surfaces of cancers. This allows diseased cells to evade detection by the immune system.
Most patients (70%) with mucosal melanoma had PD-L1 positive tumors.
"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 Butler.
"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."
Notably, patients who had received ipilimumab, a monoclonal antibody therapy, could still benefit from pembrolizumab.1
In KEYNOTE-045, a phase 3 trial addressing bladder cancer, researchers demonstrated that pembrolizumab treatment resulted in longer OS with fewer side effects compared with patients who had received chemotherapy.2
Median OS was 10.3 months with pembrolizumab vs 7.4 months with chemotherapy. Additionally, more patients who received pembrolizumab responded to treatment, and their response lasted longer than chemotherapy.
“The objective response rate, the percentage of patients whose tumors shrank or disappeared, was almost twice as high with pembrolizumab: 21% compared to 11% on chemotherapy,” explained Andrea Necchi, MD, attending physician in the Department of Medical Oncology at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
The lower incidence of treatment-related side effects could particularly benefit a primarily elderly population.2
1. 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. Paper presented at: European Cancer Congress 2017; January 27-30, 2017; Amsterdam, Netherlands. Abstract 1142.
2. Necchi A, Bellmunt J, de Wit R, et al. Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: phase 3 KEYNOTE-045 study. Paper presented at: European Cancer Congress 2017; January 27-30, 2017; Amsterdam, Netherlands. Abstract 3LBA.