Phase 2 trial of pemetrexed and pembrolizumab for recurrent and/or metastatic nonadenoid cystic saliva gland cancer

Treatment options for patients with recurrent and/or metastatic saliva gland cancer (R/M SGC) are limited. The phase 2 MC200708 trial at the Mayo Clinic (Rochester, MN) evaluated the combination of pemetrexed and pembrolizumab for R/M SGC. Results from the nonadenoid cystic carcinoma (ACC) cohort have now been published. Patients received 3-week cycles of intravenous pemetrexed 500 mg/m² plus pembrolizumab 200 mg until progression or intolerance. Primary endpoint was objective response rate (ORR). Among 24 evaluable patients, 9 had a confirmed response (ORR 37.5%; 95% CI 18.8-59.4), whereas the ORR among patients with salivary duct carcinoma (SDC) was 63.6%. Median duration of response was 15.3 months (95% CI 12.4-NR), median progression-free survival was 6.2 months (2.1-17.3), median overall survival was 20.0 months (17.1-NR), with 1-year PFS and OS rates 36.1% (21.0-62.2) and 71.9% (55.0-94.0), respectively. Seven patients (29.2%) had grade 3 to 4 toxicity, the majority hematologic. The authors conclude that the combination of pemetrexed and pembrolizumab has promising and durable activity in patients with R/M SGC, with notable responses in patients with SDC.