Rezvilutamide + ADT delivers improved outcomes for mHSPC patients regardless of age

The combination of rezvilutamide plus androgen-deprivation therapy (ADT) proves to be efficacious and well-tolerated in the treatment of patients with high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC) across all age groups, according to a post hoc analysis of the phase III CHART trial.

Results for all efficacy outcomes favoured rezvilutamide plus ADT over bicalutamide plus ADT in the ≤64-, 65–74-, and ≥75-year age groups, reported one of the study authors Dr Xuefeng Qiu from the Drum Tower Hospital, Medical School of Nanjing University in Nanjing, China.

Compared with bicalutamide plus ADT, rezvilutamide plus ADT prolonged radiographic progression-free survival (rPFS), with reductions of between 49 percent and 56 percent in the risk of radiographic progression or death (≤64 years: hazard ratio [HR], 0.44, 95 percent confidence interval [CI], 0.26–0.74; 65–74 years: HR, 0.45, 95 percent CI, 0.31–0.65; ≥75 years: HR, 0.51, 95 percent CI, 0.31–0.85) relative to bicalutamide plus ADT. [ESMO Asia 2024, abstract 337MO)

The same was true for overall survival (OS), with the risk of all-cause death decreasing by between 17 percent and 47 percent with rezvilutamide plus ADT vs bicalutamide plus ADT (≤64 years: HR, 0.83, 95 percent CI, 0.48–1.44; 65–74 years: HR, 0.43, 95 percent CI, 0.28–0.67; ≥75 years: HR, 0.66, 95 percent CI, 0.40–1.07).

Additionally, rezvilutamide plus ADT delayed prostate-specific antigen (PSA) progression (≤64 years: HR, 0.21, 95 percent CI, 0.13–0.34; 65–74 years: HR, 0.25, 95 percent CI, 0.17–0.36; ≥75 years: HR, 0.14, 95 percent CI, 0.08–0.26), as well as increased the percentage of patients achieving undetectable PSA levels (≤64 years: 71.4 percent vs 28.1 percent; 65–74 years: 65.2 percent vs 39.7 percent; ≥75 years: 72.8 percent vs 29.0 percent) when compared with bicalutamide plus ADT.

When analyses were limited to the subgroup of older patients with poor health status (≥75 years and ECOG PS of 1), rPFS, OS, and time to PSA progression were all longer with rezvilutamide plus ADT vs the comparator.

Safety profile

“The safety profiles of rezvilutamide plus ADT and bicalutamide plus ADT were generally similar across the three age groups, as well as in older patients with poor health status, despite the longer duration of exposure to rezvilutamide plus ADT treatment (2.0–2.3 times longer than bicalutamide plus ADT),” Qiu noted.

Across the ≤64-, 65–74-, and ≥75-year age groups, the percentage of patients with treatment-related adverse events (TRAEs) ranged from 81.3 percent to 82.9 percent with rezvilutamide plus ADT and from 76.4 percent to 79.0 percent with bicalutamide plus ADT. Treatment-related serious adverse events occurred in 13 rezvilutamide-treated patients and in 10 of those who received bicalutamide.

Overall, TRAEs led to treatment discontinuation in three patients each in the rezvilutamide and bicalutamide arms. One patient treated with bicalutamide plus ADT in the ≥75-year age group died due to a TRAE.

“Rezvilutamide is a novel orally administered androgen receptor inhibitor that targets the androgen-receptor axis, a key driver of prostate cancer growth and progression,” Qiu said. “This post hoc analysis supports its use as a treatment option for high-volume mHSPC, regardless of age.” [Lancet Oncol 2022;23:e490; Drugs 2023;83:189-193]

A total of 654 patients with high-volume mHSPC and no prior chemotherapy or other localized treatment for prostate cancer were included in CHART. These patients were randomly assigned to receive either rezvilutamide 240 mg plus ADT or bicalutamide 50 mg plus ADT orally once daily.

Of the patients, 173 were in the ≤64-year age group, 307 were in the 65–74-year age group, and 174 in the ≥75-year age group. Baseline characteristics were generally similar among age groups, except for a lower percentage of patients with ECOG PS of 1 in the ≤64-year age group (64.2 percent) than in the other two age groups (65–74 years, 73.6 percent; ≥75 years, 83.9 percent)

The CHART trial led to the approval of rezvilutamide plus ADT for high-volume mHSPC in China in 2022.