Patients with androgen receptor (AR)–positive salivary gland carcinoma treated with darolutamide plus goserelin experienced greater antitumor activity than those treated with darolutamide alone in the Japanese phase II DISCOVARY trial, while both approaches demonstrated manageable safety profiles and preserved health-related quality of life. The findings, published in the Journal of Clinical Oncology, were reported by Okano et al.
Study Details
DISCOVARY, a prospective, open-label, multicenter study, was conducted at 12 institutions in Japan. The trial enrolled 57 adults with unresectable locally advanced or recurrent/metastatic AR-positive salivary gland carcinoma into two sequential, nonrandomized cohorts. The first cohort received darolutamide monotherapy at 600 mg twice daily (n = 24), whereas the second cohort received darolutamide plus goserelin at 3.6 mg every 28 days (n = 33). Most participants had an Eastern Cooperative Oncology Group performance status of 0 and metastatic disease, most commonly in the lungs, distant lymph nodes, and bone.
The primary endpoint was objective response rate, with secondary endpoints including progression-free survival, overall survival, duration of response, clinical benefit rate, safety, and health-related quality of life. The investigators emphasized that the sequential design was intended to evaluate two treatment strategies independently and was not powered for direct comparisons between cohorts.
Key Results
Darolutamide monotherapy produced a confirmed objective response rate of 8.3% (90% confidence interval [CI] = 1.5%–24.0%), with two partial responses and no complete responses. Median progression-free survival was 5.7 months, and the 12-month overall survival rate was 91.3%.
In contrast, darolutamide plus goserelin achieved a centrally assessed objective response rate of 45.2% (90% CI = 29.7%–61.3%), including 1 complete response and 13 partial responses, meeting the study’s primary endpoint. The combination cohort also demonstrated a median progression-free survival of 13.1 months and a 12-month overall survival rate of 87.0%. Clinical benefit rates were 41.7% with monotherapy and 51.6% with combination therapy, while disease control rates were 54.2% and 64.5%, respectively.
Grade 3 or higher adverse events occurred in 37.5% of patients receiving monotherapy and 18.2% receiving combination therapy. No treatment-related deaths or grade 5 adverse events were observed in either cohort. Health-related quality of life—assessed with EQ-5D-5L and EQ-VAS instruments—was generally maintained throughout treatment, with no consistent clinically meaningful deterioration reported.
The investigators concluded: “Darolutamide demonstrated antitumor activity in AR-positive [salivary gland carcinoma], with numerically more favorable outcomes with goserelin. Darolutamide plus goserelin may represent a chemotherapy-sparing option in this rare malignancy.”
Makoto Tahara, MD, PhD, of the Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Bayer Yakuhin, Ltd. For full disclosures of the study authors, visit ascopubs.org.
