As reported in The Lancet Oncology by Gu et al, interim analyses of the phase III CHART trial have shown improved radiographic progression-free survival and overall survival with the novel androgen receptor inhibitor rezvilutamide vs bicalutamide when both were combined with androgen-deprivation therapy (ADT) in patients with high-volume metastatic hormone-sensitive prostate cancer.  

Study Details

The open-label trial included 654 patients from sites in China, Poland, Czech Republic, and Bulgaria. They were randomly assigned between June 2018 and August 2020 to receive ADT (surgical ADT, luteinizing hormone-releasing hormone agonist, or antagonist) plus either rezvilutamide at 240 mg (n = 326) or bicalutamide at 50 mg (n = 328) once daily in 28-day treatment cycles until disease progression or unacceptable toxicity. The dual primary endpoints were radiographic progression-free survival assessed by blinded independent review committee and overall survival in the intention-to-treat population. Overall, 90% of patients in each group were from China. 

Progression-Free and Overall Survival

At the preplanned interim analysis for radiographic progression-free survival, median follow-up was 21.2 months (interquartile range [IQR] = 16.6­–25.8 months). Median radiographic progression-free survival was not reached (95% CI = not reached–not reached) in the rezvilutamide group vs 25.1 months (95% CI = 15.7 months–not reached) in the bicalutamide group (hazard ratio [HR] = 0.44, 95% CI = 0.33–0.58, P < .0001). Rates at 2 years were 72.3% vs 50.0%. Hazard ratios were 0.40 (95% CI = 0.30–0.54) among patients from China and 0.87 (95% CI = 0.39–1.96) among those from other regions.

At the preplanned interim analysis for overall survival, median follow-up was 29.3 months (IQR = 21.0–33.3 months). Death had occurred in 25% of patients in the rezvilutamide group vs 38% of patients in the bicalutamide group (HR = 0.58, 95% CI = 0.44–0.77, P = .0001). Median overall survival was not reached (95% CI = not reached to not reached) vs not reached (95% CI = 36.2 months to not reached). Rates at 2 years were 81.6% vs 70.3%. Hazard ratios were 0.55 (95% CI = 0.40–0.74) among patients from China and 0.85 (95% CI = 0.39–1.87) among patients from other regions.

Adverse Events

The most common grade ≥ 3 adverse events in the rezvilutamide group were hypertension (8% vs 7% of the bicalutamide group), hypertriglyceridemia (7% vs 2%), increased body weight (6% vs 4%), anemia (4% vs 5%), and hypokalemia (3% vs 1%). Serious adverse events were reported in 28% vs 21% of patients and were considered related to treatment in 4% vs 3%. Adverse events led to discontinuation of treatment in 2% of patients in each group. One treatment-related death was observed, due to an unknown specific cause in a patient in the bicalutamide group.

The investigators concluded, “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.”

Dingwei Ye, MD, of the Department of Urology, Fudan University Shanghai Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Jiangsu Hengrui Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.