A phase II basket trial of DART SWOG S1609: the salivary gland tumor cohort.

内容摘要

Anti-programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 antibodies are efficacious in various malignancies. The potential role of dual checkpoint inhibitors in many rare solid tumors is not established. This study presents the results of ipilimumab-nivolumab in salivary gland neoplasm cohorts of the SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) trial. DART is a prospective, open-label, multicenter (1016 US sites), multi-cohort phase II trial of ipilimumab (1 mg/kg intravenously (IV) every 6 weeks) plus nivolumab (240 mg IV every 2 weeks). We performed a prospective, multicenter phase II clinical trial of ipilimumab (1 mg/kg IV every 6 weeks) plus nivolumab (240 mg IV every 2 weeks) in three salivary gland neoplasm cohorts: major and minor salivary gland and adenoid cystic cancers. Patients with adenoid cystic salivary gland tumors (N = 26) and other salivary gland neoplasms (N = 34) were evaluable. The most common site of origin was the parotid (31%, N = 8 adenoid cystic group; 68%, N = 23 remaining histologies). In the adenoid cystic group, objective response rate (ORR), 4% (complete response (CR) 0%, N = 0; partial response (PR) 4%, N = 1); 6-month progression-free survival (PFS) and overall survival (OS), 32% (95% confidence interval (CI) 18%-57%) and 84% (95% CI 71%-100%), respectively. In the remaining histologic subtypes, the confirmed ORR was 9% (CR, 0%, N = 0; PR, 9%, N = 3); stable disease (SD) >6 months/PR/unconfirmed PR = 35%; 6-month PFS and OS, 34% (95% CI 21%-55%) and 88% (95% CI 78%-100%), respectively. The most common toxicities were fatigue (39%) and diarrhea (26%); diarrhea (8%) was the most common grade 3-4 immune-related adverse event. In salivary gland tumors, combined ipilimumab plus nivolumab resulted in only a 4% ORR in adenoid cystic carcinoma and 9% in all other histologies combined, though the latter showed clinical benefit (included SD >6 months) in 35% of patients.Trial registration: ClinicalTrials.gov registry: NCT02834013. Testing a dual immunotherapy treatment for rare salivary gland cancers Salivary gland cancers are rare, and there are limited treatment options for patients whose cancer has spread or returned after initial treatment. Immunotherapy helps the immune system fight cancer and has been successful in some other types of cancer. This study tested whether a combination of two immunotherapy drugs—one targeting CTLA-4 and the other targeting PD-1—could help treat these rare tumors. Patients with advanced salivary gland cancer took part in a clinical trial called DART. They received the two immunotherapy drugs and were monitored to see if their tumors shrank or stopped growing. Researchers also tracked any side effects caused by the treatment. Some patients responded well to the treatment, where their tumors got smaller or stopped growing for a period of time. However, not all patients benefited. Some experienced side effects, as the immune system can also attack healthy cells. This study shows that dual immunotherapy may be a promising option for some people with rare salivary gland cancers, but more research would be needed to understand who is most likely to benefit and how to manage side effects. The findings could help doctors develop better treatment strategies for these rare cancers in the future.