| Affiliation: | 1. Department of Urology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China;2. Department of Urology, Changzheng Hospital, Naval Medical University, Shanghai, China;3. Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China;4. Department of Urology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China;5. Department of Urology, Huadong Hospital, Fudan University, Shanghai, China;6. Department of Urology, Peking University First Hospital, Beijing, China;7. Department of Urology, 307 Hospital of People's Liberation Army, Beijing, China;8. Department of Urology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China;9. Department of Urology, The First Affiliated Hospital of the Medical School of Zhejiang University, Hangzhou, China;10. Department of Urology, Jiangxi Province People's Hospital, Nanchang, China;11. Department of Urology, Guangxi Tumor Hospital, Nanning, China;12. Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan, China;13. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;14. Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;15. Department of Urology, Peking University Cancer Hospital and Institute, Beijing, China;16. Department of Urology, The First Affiliated Hospital, Dalian Medical University, Dalian, China;17. Department of Urology, Liaoning Cancer Hospital & Institute, Shenyang, China;18. Department of Urology, Second Xiangya Hospital, Central South University, Changsha, China;19. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China |
| Abstract: | We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177). |
