Addition of Rezvilutamide to ADT Improves OS and rPFS Vs Bicalutamide/ADT in Hormone-Sensitive Prostate Cancer

Rezvilutamide with androgen-deprivation therapy yielded improved overall survival and radiographic progression-free survival compared with bicalutamide and androgen-deprivation therapy in patients with high-volume metastatic hormone-sensitive prostate cancer.

Treatment with rezvilutamide plus androgen-deprivation therapy (ADT) produced improvements in the co-primary end points of radiographic progression-free survival (rPFS) and overall survival (OS) compared with bicalutamide (Casodex) plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, according to data from the phase 3 CHART trial (NCT03520478).

With a median follow-up of 21.2 months (interquartile range, 16.6-25.8), the median rPFS was not reached (NR; 95% CI, NR-NR) for patients receiving rezvilutamide and 25.1 months (95% CI, 15.7-NR) for those receiving bicalutamide (HR, 0.44; 95% CI, 0.33-0.58; P <.0001). At a median follow-up of 29.3 months (interquartile range, 21.0-33.3), the trial investigators reported that OS was significantly longer in the rezvilutamide cohort compared with the bicalutamide group (HR, 0.58; 95% CI, 0.44-0.77; P = .0001). The median OS was not reached in the rezvilutamide cohort (95% CI, NR-NR) or the bicalutamide cohort (95% CI, 36.2-NR). The 2-year OS rates for the rezvilutamide and bicalutamide groups, respectively, were 81.6% (95% CI, 76.9%-85.4%) and 70.3% (95% CI, 64.9%-75.1%).

The randomized, open-label phase 3 CHART trial enrolled a total of 654 patients who were randomly assigned to receive ADT with either 240 mg of rezvilutamide (n = 326) or 50 mg of bicalutamide (n = 328) taken orally once daily in 28-day treatment cycles until disease progression, unacceptable toxicity, or patient withdrawal. Secondary end points of the trial included investigator-assessed rPFS, time to prostate-specific antigen (PSA) progression, time to next skeletal-related event, and objective response rate (ORR). Exploratory end points included PSA response rate and undetectable PSA rate.

Patients with high-volume disease, defined as the presence of 4 or more bone lesions with at least 1 lesion beyond the pelvis or vertebral column, were eligible to enroll on the trial. Additional inclusion criteria included having an ECOG performance status of 0 or 1 as well as adequate organ function.

At baseline, the median age of enrolled patients across both treatment cohorts was 69 years. In the rezvilutamide and bicalutamide cohorts, respectively, most patients were younger than 70 years (52% vs 51%), Asian (90% vs 90%), from China (90% vs 90%), had an ECOG performance status of 1 (74% vs 73%), and had a Gleason score of 8 or more (85% vs 78%). Moreover, the majority of patients did not have visceral metastases (80% vs 79%), had metastatic disease of the bone and soft tissue (60% vs 61%), and did not have lactic acid dehydrogenase above the normal upper limit (75% vs 80%).

Investigators of the trial reported a generally consistent rPFS benefit in the rezvilutamide cohort compared with the bicalutamide cohort across most subgroups with the exception of those with visceral metastases and who were not from China.

The investigator assessed ORR and the undetectable PSA rates in the rezvilutamide and bicalutamide cohorts, respectively, were 81.0% (95% CI, 74.2%) vs 67.9% (95%CI, 60.0-75.2%) and 68.7% (95% CI, 63.4%-73.7%) vs 33.5% (95% CI, 28.4%-38.9%). Additionally, the PSA response rate was 94.4% (95% CI, 89.3%-97.6%) vs 78.9% (95% CI, 71.2%-85.3%) in each respective group.

The most common grade 3 or higher adverse effects (AEs) in the rezvilutamide and bicalutamide groups, respectively, included hypertension (8% vs 7%), hypertriglyceridemia (7% vs 2%), increased weight (6% vs 4%), anemia (4% vs 5%), and hypokalemia (3% vs 1%). No treatment-related deaths occurred in the rezvilutamide cohort, and 1 treatment-related death of an unknown specific cause occurred in the bicalutamide cohort. Overall, trial investigators reported that the safety profiles observed in this study were consistent with those documented in other trials involving rezvilutamide.


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 randomised, open-label, phase 3 trial. Lancet Oncol. Published online September 5, 2022. doi:10.1016/S1470-2045(22)00507-1