Mucosal melanoma is an aggressive melanoma with poor prognosis.,We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), −002 (NCT01704287), and −006 (NCT01866319).,Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W.,Response was assessed by independent central review per RECIST v1.1.,1567 patients were treated and 84 (5%) had mucosal melanoma.,Fifty-one of 84 were ipilimumab-naive.,In patients with mucosal melanoma, the objective response rate (ORR) was 19% (95% CI 11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6).,Median progression-free survival (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6).,ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in ipilimumab-naive and ipilimumab-treated patients.,Pembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab.
Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma1, and because mesothelioma clustering is observed in some families1, we searched for genetic predisposing factors.,We discovered germline mutations in BAP1 (BRCA1-associated protein 1) in two families with a high incidence of mesothelioma.,Somatic alterations affecting BAP1 were observed in familial mesotheliomas, indicating biallelic inactivation.,Besides mesothelioma, some BAP1 mutation carriers developed uveal melanoma.,Germline BAP1 mutations were also found in two of 26 sporadic mesotheliomas: both patients with mutant BAP1 were previously diagnosed with uveal melanoma.,Truncating mutations and aberrant BAP1 expression were common in sporadic mesotheliomas without germline mutations.,These results reveal a BAP1-related cancer syndrome characterized by mesothelioma and uveal melanoma.,We hypothesize that other cancers may also be involved, and that mesothelioma predominates upon asbestos exposure.,These findings will help identify individuals at high risk of mesothelioma who could be targeted for early intervention.