Rezvilutamide vs Bicalutamide + ADT for Hormone Sensitive Prostate Cancer

The novel androgen-receptor inhibitor, Rezvilutamide, has demonstrated potent antitumor activity against metastatic castration-resistant prostate cancer. It has low blood-brain barrier penetration. This study aimed to assess the effectiveness and safety of rezvilutamide compared to bicalutamide when used in conjunction with androgen-deprivation therapy (ADT) for patients with high-volume, metastatic, hormone-sensitive prostate cancer. The phase 3 trial was conducted at 72 medical facilities across China, Poland, the Czech Republic, and Bulgaria. It was a randomized and open-label study. The inclusion criteria for the study were patients 18 or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. They were diagnosed with high-volume metastatic, hormone-sensitive prostate cancer. Prior history of chemotherapy or any other form of localized therapy for prostate cancer was contraindicated. The study involved a randomized assignment of patients in a 1:1 ratio to receive either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily in addition to ADT. The randomization process was carried out using an interactive response technology system with a block size of four. Stratification was performed based on ECOG performance status and visceral metastasis, except lymph nodes. The following report showcases the findings of the prearranged interim analyses for the two co-primary endpoints of radiographic progression-free survival evaluated by a blinded independent review committee and overall survival in the intention-to-treat population. The safety of all patients who received at least one dose of the study medication was evaluated. The current investigation remains in progress. However, the recruitment phase has been terminated.

During the period spanning from June 28, 2018, to Aug 6, 2020, a total of 792 patients underwent screening, out of which 654 patients were subjected to random assignment. These patients were then divided into two groups, one receiving rezvilutamide plus ADT (n=326) and the other receiving bicalutamide plus ADT (n=328). At the premeditated interim analysis for radiographic progression-free survival, with a data cutoff of May 16, 2021, the median duration of follow-up was 21.2 months (interquartile range 16.6-25.8). The administration of Rezvilutamide resulted in a significant enhancement of radiographic progression-free survival compared to bicalutamide. The median radiographic progression-free survival was not reached (95% CI did not reach – not reached) in the Rezvilutamide group, while it was 25.1 months (95% CI 15.7 – not reached) in the bicalutamide group. The hazard ratio (HR) was 0.44 (95% CI 0.33 – 0.58), and the P< 0.0001. At the pre-determined interim analysis for the assessment of overall survival (with a data cutoff date of February 28, 2022), the median duration of follow-up was 29.3 months (with an interquartile range of 21.0 to 33.3). The administration of Rezvilutamide resulted in a significant enhancement of the patient’s overall survival compared to bicalutamide. The hazard ratio was 0.58 (95% confidence interval: 0.44-0.77), and the P= 0.0001. The median overall survival was not reached (95% confidence interval: not reached – not reached) for the Rezvilutamide group, while it was not reached (36.2 – not reached) for the bicalutamide group. The safety population experienced grade 3 or worse adverse events of various causes. The most common adverse events were hypertension, hypertriglyceridemia, increased weight, anemia, and hypokalemia. In the rezvilutamide group, 8% of the 323 patients experienced hypertension, 7% experienced hypertriglyceridemia, 6% experienced increased weight, 4% experienced anemia, and 3% experienced hypokalemia. In the bicalutamide group, 7% of the 324 patients experienced hypertension, 2% experienced hypertriglyceridemia, 4% experienced increased weight, 5% experienced anemia, and 1% experienced hypokalemia. Ninety patients (28%) in the rezvilutamide cohort and sixty-nine patients (21%) in the bicalutamide cohort reported serious adverse events. There were no instances of treatment-associated mortality observed in the cohort receiving rezvilutamide. Conversely, the bicalutamide group experienced one case of treatment-related death with an unknown etiology, which accounted for less than 1% of the total group.

Source: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00507-1/fulltext

Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT03520478

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, Prof Xiaojing Zhang, Prof Dingwei Ye/Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomized, open-label, phase 3 trial/doi.org/10.1016/S1470-2045(22)00507-1