Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial.

Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer.

CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478.

Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group.

In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile.

Jiangsu Hengrui Pharmaceuticals.

The Lancet. Oncology. 2022 Sep 05 [Epub ahead of print]

Weijie Gu, Weiqing Han, Hong Luo, Fangjian Zhou, Dalin He, Lulin Ma, Hongqian Guo, Chaozhao Liang, Tie Chong, Jun Jiang, Zhiwen Chen, Yong Wang, Qing Zou, Ye Tian, Jun Xiao, Jian Huang, Shaoxing Zhu, Qiang Dong, Xiaoping Zhang, Hanzhong Li, Xinfeng Yang, Chunxia Chen, Junliang Li, Chunlei Jin, Xiaojing Zhang, Dingwei Ye, CHART Investigators

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China., Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Center, Changsha, China., Department of Urology, Chongqing University Cancer Hospital, Chongqing Cancer Hospital, Chongqing, China., Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China., Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Department of Urology, Peking University Third Hospital, Beijing, China., Department of Urology, Nanjing Drum Tower Hospital, Nanjing, China., Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, China., Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Department of Urology, Daping Hospital of Army Medical University, Chongqing, China., Department of Urology, The Southwest Hospital of Army Medical University, Chongqing, China., Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China., Department of Urology, Jiangsu Cancer Hospital, Nanjing, China., Department of Urology, Beijing Friendly Hospital of Capital Medical University, Beijing, China., Department of Urology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei, China., Department of Urology, Sun Yat-Sen Memorial Hospital Sun Yat-Sen University, Guangzhou, China., Department of Urology, Zhejiang Cancer Hospital, Hangzhou, China., Department of Urology, West China Hospital, Sichuan University, Chengdu, China., Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals, Shanghai, China., Department of Urology, Peking Union Medical College Hospital, Beijing, China., Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China. Electronic address: .