Multicenter phase 2 trial of darolutamide with or without goserelin in androgen receptor-positive salivary gland carcinoma

Salivary gland carcinoma (SGC) is an aggressive malignancy with no standard systemic treatment. In salivary duct carcinoma, androgen receptor (AR) expression in frequently observed, suggesting that inhibition of the AR pathway could be a therapeutic strategy. The multicenter phase 2 DISCOVARY trial in Japan evaluated the second-generation AR signaling inhibitor darolutamide with or without goserelin for patients with AR-positive unresectable locally advanced (LA) or recurrent/metastatic (R/M) SGC. Patients in the monotherapy cohort (n=24) received darolutamide 600 mg orally twice daily; patients in the combination cohort (n=33) received darolutamide 600 mg orally twice daily plus goserelin 3.6 mg subcutaneously once every 28 days. The primary endpoint was objective response rate. The objective response rate was 45.2% (90% CI 29.7-61.3) in the combination cohort (panel A) and 8.3% (1.5-24.0) in the monotherapy cohort (panel B). The median progression-free survival was 13.1 months in the combination cohort and 5.7 months in the monotherapy cohort. Most adverse events were grade 1 or 2 in severity, with no treatment-related deaths. Quality of life was preserved. The authors conclude that darolutamide plus goserelin may represent a chemotherapy-sparing option for AR-positive advanced SGC.