The phase 3 CHART study reveals better survival with rezvilutamide plus androgen deprivation therapy vs bicalutamide and androgen deprivation therapy in metastatic, hormone-sensitive prostate cancer.
Rezvilutamide (SHR3680) plus androgen deprivation therapy (ADT) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared with bicalutamide (Casodex) plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer.1
Findings come from the randomized, open-label, phase 3 CHART study (NCT03520478) which evaluated the efficacy and safety of rezvilutamide vs bicalutamide in combination with ADT in this patient population. On top of improved OS and rPFS, the combination of rezvilutamide and ADT demonstrated a tolerable safety profile.
Rezvilutamide is a novel androgen-receptor inhibitor with low blood–brain barrier penetration. Previous studies of rezvilutamide have demonstrated potent antitumour activity against metastatic castration-resistant prostate cancer.
The phase 3 study enrolled patients at 72 hospitals across China, Poland, Czech Republic, and Bulgaria.2 Patients were eligible for enrollment if they were male, aged 18 years or older, had an ECOG performance status of 0 or 1, a diagnosis of high-volume metastatic, hormone-sensitive prostate cancer, and had adequate hepatic, renal, heart, and hematological function. Patients who received previous chemotherapy or other localized treatment for prostate cancer were not included.
Patients were randomly assigned in a 1:1 ratio and administered either ADT plus rezvilutamide 240 mg or bicalutamide 50 mg orally once daily. Randomization was performed via an interactive response technology system and patients were stratified according to ECOG performance status and presence of visceral metastasis. This excluded lymph nodes.
The primary end points of the study were rPFS and OS and investigators evaluated the secondary end points of time to prostate specific antigen progression, time to skeletal-related events, objective, and time to initiation of a new antineoplastic therapy response rate.
A total of 792 patients were screened between June 28, 2018, and August 6, 2020, with 654 patients randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328).
At the data cutoff of May 16, 2021, results from the pre-planned interim analysis for rPFS showed that the median follow-up duration was 21.2 months (interquartile range [IQR], 16.6-25.8). The rPFS with rezvilutamide was significantly improved vs the rPFS with bicalutamide (median rPFS not reached [95% CI, not reached [NR]-NR] vs 25.1 months [95% CI, 15.7-NR]; HR 0.44; 95% CI, 0.33-0.58; P < .0001).
The preplanned interim analysis for overall survival had a data cutoff of February 28, 2022. Here, the median follow-up duration was 29.3 months (IQR 21.0-33.3), and treatment with rezvilutamide significantly improved OS vs treatment with bicalutamide (HR 0.58; 95% CI, 0.44-0.77; P = .0001). Additionally, the median OS with rezvilutamide was not reached (95% CI, NR-NR) vs not reached (36.2-NR) with bicalutamide.
Frequently reported grade 3 or greater adverse events (AEs) in the safety population included hypertension (8% with rezvilutamide vs 7% with bicalutamide), hypertriglyceridemia (7% vs 2%), increased weight (6% vs 4%), anemia (4% vs 5%), and hypokalaemia (3% vs 1%). Serious AEs were observed in 28% of patients given rezvilutamide and 21% of patients administered bicalutamide. There were no deaths related to treatment in the rezvilutamide group. However, 1 treatment-related death of unknown specific cause occurred in a patient given bicalutamide.
Overall, this interim analysis demonstrated rezvilutamide plus ADT to significantly improve rPFS and OS vs bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, and a tolerable safety profile was seen.