Efficacy and safety of darolutamide in Chinese patients with metastatic hormone-sensitive prostate cancer (mHSPC): A subpopulation analysis of the phase 3 ARASENS study.

person Shanshan Wang Fudan University Shanghai Cancer Center, Shanghai, China info_outline Shanshan Wang, Cheng Fu, Qing Zou, Youyuan Li, Dalin He, Shaogang Wang, Hongkai Wang, Matthew Raymond Smith, Bertrand F. Tombal, Maha H. A. Hussain, Yi Niu, Ling Cai, Nan Hu, Shiyun Huang, Shivani Kapur, Rui Li, Iris Kuss, Dingwei Ye

Authors person Shanshan Wang Fudan University Shanghai Cancer Center, Shanghai, China info_outline Shanshan Wang, Cheng Fu, Qing Zou, Youyuan Li, Dalin He, Shaogang Wang, Hongkai Wang, Matthew Raymond Smith, Bertrand F. Tombal, Maha H. A. Hussain, Yi Niu, Ling Cai, Nan Hu, Shiyun Huang, Shivani Kapur, Rui Li, Iris Kuss, Dingwei Ye Organizations Fudan University Shanghai Cancer Center, Shanghai, China, Liaoning Tumour Hospital, Shenyang, China, Jiangsu Cancer Hospital, Nanjing, China, Hubei Cancer Hospital, Wuhan, China, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium, Northwestern University, Feinberg School of Medicine, Chicago, IL, Bayer Healthcare Company Ltd., Beijing, China, Bayer Healthcare Co Ltd, Beijing, China, Bayer SEA, Singapore, Singapore, Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, Bayer AG, Berlin, Germany, Fudan University Shanghai Cancer Center, Shanghai, Xuhui District, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bayer and Orion Corporation Background: Darolutamide (DARO) is an androgen receptor inhibitor approved in China for the treatment of nonmetastatic castration-resistant prostate cancer (CRPC). In the global ARASENS trial, DARO significantly increased overall survival (OS) vs placebo (PBO) in patients (pts) with mHSPC. The efficacy and safety of DARO in the Chinese subpopulation of ARASENS are reported here. Methods: In this randomized, double-blind phase 3 trial, 1305 pts with mHSPC were randomized 1:1 to receive DARO 600 mg orally twice daily or PBO, in combination with androgen-deprivation therapy (ADT) and docetaxel. The primary endpoint was OS. Results: In mainland China, 202 pts were randomized to the DARO group (n = 104) or the PBO group (n = 98). Demographics and baseline characteristics were well balanced between treatment groups and comparable to the overall ARASENS population, except for a slightly higher proportion of pts with Gleason score ≥8, higher proportion with metastatic disease at diagnosis, and higher median baseline prostate-specific antigen (PSA) in Chinese pts vs the overall population. The risk of death was reduced by 36% (HR 0.64, 95% CI 0.41–0.99) with DARO vs PBO in Chinese pts (Table). The key secondary endpoint time to CRPC (HR 0.32, 95% CI 0.20–0.50) and the exploratory endpoint time to PSA progression (HR 0.22, 95% CI 0.13–0.37) also favored DARO. In the DARO group, 81% of pts had a maximum PSA decline of ≥90% from baseline (PSA90) at week 12, while 88% had PSA90 and 71% reached PSA < 0.2 ng/mL at any time. Incidences of treatment-emergent adverse events (TEAEs) in Chinese pts were similar between treatment groups and comparable to the overall population. The most common grade 3/4 TEAE in Chinese pts was neutropenia (DARO 64%, PBO 62%), a known toxicity of docetaxel; grade 3/4 febrile neutropenia occurred in 4.0% of Chinese pts compared with 7.6% in the overall population. Conclusions: In the ARASENS subpopulation of Chinese pts with mHSPC, DARO + ADT + docetaxel showed favorable efficacy and safety vs PBO + ADT + docetaxel: OS and clinically relevant secondary endpoints favored DARO vs PBO, and the incidences of TEAEs were similar in the two treatment groups. These results are consistent with the findings reported for the overall population in ARASENS. Clinical trial information: NCT02799602. Key efficacy results for the ARASENS Chinese subpopulation. Endpoints DARO + ADT + docetaxel (n = 104) PBO + ADT + docetaxel (n = 98) HR (95% CI) OS, median (95% CI) months NE (47.9–NE) 44.9 (37.4–NE) 0.64 (0.41–0.99) Time to CRPC, median (95% CI) months NE (NE–NE) 16.6 (13.8–22.1) 0.32 (0.20–0.50) Time to PSA progression, median (95% CI) months NE (NE–NE) 19.4 (14.0–24.6) 0.22 (0.13–0.37) PSA response at any time, n (%) PSA90 91 (88) 68 (69) PSA < 0.2 ng/mL 74 (71) 19 (19) NE, not estimable.

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