Rezvilutamide Improves Survival vs Bicalutamide in Metastatic Hormone-Sensitive Prostate Cancer

In 2 interim analyses of the phase 3 CHART trial, rezvilutamide plus androgen-deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) in patients with high-volume, metastatic, hormone-sensitive prostate cancer when compared to bicalutamide plus ADT. Rezvilutamide is a novel androgen-receptor inhibitor with low blood-brain barrier penetration that has “shown potent antitumor activity against metastatic castration-resistant prostate cancer,” as lead investigator Weijie Gu, MD, Fudan University Shanghai Cancer Center, Shanghai, China, and coauthors wrote.

The international, multicenter, open-label CHART study enrolled 654 patients with high-volume, metastatic, hormone-sensitive prostate cancer who had not received previous chemotherapy or localized treatment for prostate cancer between June 28, 2018, and August 6, 2020. Patients were randomized on a 1:1 basis to receive ADT plus either 240 mg rezvilutamide (n = 326), or 50 mg bicalutamide (n = 328), orally once daily.

The 2 coprimary end points of the study were rPFS and OS in the intention-to-treat population. Safety was also assessed, in all patients who received ≥1 dose of rezvilutamide. The current report shares data from 2 preplanned interim analyses.

With a median follow-up duration was 21.2 months, PFS was significantly improved for those patients treated with rezvilutamide (median PFS, not reached; 95% confidence interval [CI], not reached to not reached), compared to those treated with bicalutamide (median PFS, 25.1 months; 95% CI 15.7 to not reached; hazard ratio [HR], 0.44; 95% CI, 0.33 to 0.58; P <.0001).

With a median follow-up duration of 29.3 months, OS was also significantly improved for those patients treated with rezvilutamide (median OS not reached, 95% CI, not reached to not reached), compared to those treated with bicalutamide (median OS, not reached; 95% CI, 36.2 to not reached; HR, 0.58, 95% CI, 0.44 to 0.77; P = .0001).

The most common grade ≥3 adverse events of any cause were hypertension (8% in the rezvilutamide group vs 7% in the bicalutamide group), hypertriglyceridemia (7% vs 2%), increased weight (6% vs 4%), anemia (4% vs 5%), and hypokalemia (3% vs 1%). In the rezvilutamide group, 28% of patients reported a serious adverse event, compared to 21% in the bicalutamide group. There were no treatment-related deaths in the rezvilutamide group, and 1 death of unknown specific cause in the bicalutamide group.

Dr Gu and colleagues concluded, “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.”

Source:

Gu W, Han W, Luo H, et al. 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. Lancet Oncol. 2022;23(10):1249-1260 doi:10.1016/S1470-2045(22)00507-1