Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
Darolutamide Alone and in Combination With Goserelin in Androgen Receptor-Positive Salivary Gland Carcinoma: Results From the Phase II DISCOVARY Trial.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Okano Susumu, Tahara Makoto, Tsukahara Kiyoaki, Otsuka Tomoyuki, Kano Satoshi, Nagaoka Masato, Uryu Hideoki, Sano Daisuke, Nishio Naoki, Ono Kazuchika, Ohkoshi Akira, Hanazawa Toyoyuki, Shinoda Satoru, Takeda Yuriko, Yamamoto Kouji, Kiyota Naomi
Аннотация
PURPOSE: Salivary gland carcinoma (SGC), particularly salivary duct carcinoma (SDC), is a rare and aggressive malignancy with no standard systemic treatment. Androgen receptor (AR) expression is frequently detected in SDC, which suggests inhibition of the AR pathway as a therapeutic strategy. We conducted a prospective phase II trial of the efficacy and safety of darolutamide, a second-generation AR signaling inhibitor, as monotherapy or in combination with goserelin, in patients with AR-positive unresectable locally advanced (LA) or recurrent/metastatic (R/M) SGC.
METHODS: DISCOVARY was a multicenter, single-arm, phase II trial conducted in Japan. Patients with unresectable LA or R/M AR-positive SGC were enrolled into two sequential cohorts, a monotherapy cohort (darolutamide 600 mg orally twice daily) and a combination cohort (darolutamide plus goserelin 3.6 mg subcutaneously once every 28 days). The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life.
RESULTS: Fifty-seven patients were enrolled (monotherapy, n = 24; combination, n = 33). In the monotherapy cohort, the confirmed ORR was 8.3% (90% CI, 1.5 to 24.0) and the median PFS was 5.7 months. In the combination cohort, ORR was 45.2% (90% CI, 29.7 to 61.3) and the median PFS was 13.1 months. Twelve-month OS rates were 91.3% and 87.0%, respectively. Most adverse events were grade 1 or 2 in severity, with no treatment-related deaths. Quality of life was preserved. No clear association between AR expression level or Ki-67 index and treatment response was evident in exploratory analysis.
CONCLUSION: Darolutamide demonstrated antitumor activity in AR-positive SGC, with numerically more favorable outcomes with goserelin. Darolutamide plus goserelin may represent a chemotherapy-sparing option in this rare malignancy.
METHODS: DISCOVARY was a multicenter, single-arm, phase II trial conducted in Japan. Patients with unresectable LA or R/M AR-positive SGC were enrolled into two sequential cohorts, a monotherapy cohort (darolutamide 600 mg orally twice daily) and a combination cohort (darolutamide plus goserelin 3.6 mg subcutaneously once every 28 days). The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life.
RESULTS: Fifty-seven patients were enrolled (monotherapy, n = 24; combination, n = 33). In the monotherapy cohort, the confirmed ORR was 8.3% (90% CI, 1.5 to 24.0) and the median PFS was 5.7 months. In the combination cohort, ORR was 45.2% (90% CI, 29.7 to 61.3) and the median PFS was 13.1 months. Twelve-month OS rates were 91.3% and 87.0%, respectively. Most adverse events were grade 1 or 2 in severity, with no treatment-related deaths. Quality of life was preserved. No clear association between AR expression level or Ki-67 index and treatment response was evident in exploratory analysis.
CONCLUSION: Darolutamide demonstrated antitumor activity in AR-positive SGC, with numerically more favorable outcomes with goserelin. Darolutamide plus goserelin may represent a chemotherapy-sparing option in this rare malignancy.