Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial.
Efficacy and safety of darolutamide in Japanese patients are reported here.
In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS.
In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11-0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%.
Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.
International journal of clinical oncology. 2020 Nov 23 [Epub ahead of print]
Hiroji Uemura, Hisashi Matsushima, Kazuki Kobayashi, Hiroya Mizusawa, Hiroaki Nishimatsu, Karim Fizazi, Matthew Smith, Neal Shore, Teuvo Tammela, Ken-Ichi Tabata, Nobuaki Matsubara, Masahiro Iinuma, Hirotsugu Uemura, Mototsugu Oya, Tetsuo Momma, Mutsushi Kawakita, Satoshi Fukasawa, Tadahiro Kobayashi, Iris Kuss, Marie-Aude Le Berre, Amir Snapir, Toni Sarapohja, Kazuhiro Suzuki
Department of Urology and Renal Transplantation, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan. ., Department of Urology, Tokyo Metropolitan Police Hospital, 4-22-1 Nakano, Nakano-ku, 164-8541, Japan., Department of Urology, Yokosuka Kyosai Hospital, 1-16 Yonegahamadori, Yokosuka, 238-8558, Japan., Department of Urology, National Hospital Organization, Shinshu Ueda Medical Center, 1-27-21 Midorigaoka, Ueda, 386-8610, Japan., Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-ku, 130-8587, Japan., Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805, Villejuif Cedex, France., Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA., Carolina Urologic Research Center, 823 82nd Parkway, Myrtle Beach, SC, 29572, USA., Tampere University Hospital, Urologian poliklinikka, PL 2000, Teiskontie 35, 33521, Tampere, Finland., Department of Urology, Kitasato University Hospital, 1-15-1 Kitazato Minami-ku, Sagamihara, 252-0375, Japan., Department of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan., Department of Urology, National Hospital Organization, Mito Medical Center, 280 Sakuranosato Ibarakimachi, Higashiibaraki, 311-3193, Japan., Department of Urology, Kindai University, 377-2, Onohigashi, Osakasayama, 589-8511, Japan., Department of Urology, Keio University, 35 Shinano-machi, Shinjuku-ku, 160-8582, Japan., Department of Urology, National Hospital Organization, Saitama National Hospital, 2-1 Suwa, Wako, 351-0102, Japan., Department of Urology, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi Chuo-ku, Kobe, 650-0047, Japan., Division of Urology, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan., Department of Urology, Fukui Prefectural Hospital, 2-8-1 Yotsui, Fukui, 910-8526, Japan., Clinical Statistics, Bayer AG, Building P300, B342, 13342, Berlin, Germany., Bayer Healthcare SAS, 220 Avenue de la Recherche, 59120, Loos, France., Orion Corporation Orion Pharma, Orionintie 1, P.O. Box 65, FI-02101, Espoo, Finland., Department of Urology, Gunma University, 3-39-15 Showa-machi, Maebashi, 371-8511, Japan.