The combination of the novel androgen receptor inhibitor (ARI) SHR3680 plus androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival compared with first-generation ARI bicalutamide in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), according to data from the CHART study presented at the 2022 ASCO Annual Meeting (Abstract 5005).
Ding-Wei Ye, of Fudan University Shanghai Cancer Center, China, and colleagues conducted a phase-3 trial to evaluate the superiority of a second-generation ARI compared with a first-generation ARI in high-volume mHSPC.
According to the study abstract, although previous trials had demonstrated the benefits of second-generation ARIs plus ADT compared with placebo plus ADT, there were no data comparing second-generation ARIs with first-generation ARIs.
CHART randomly assigned patients to ADT plus 240 mg per day, SHR3680 (326 patients) or 50 mg per day bicalutamide (326 patients). The primary endpoints were radiographic progression-free survival assessed by independent review committee and overall survival.
Patients assigned to SHR3680 had a significantly lower risk for radiographic progression of death compared with bicalutamide (hazard ratio [HR]=0.44; 95% CI, 0.33-0.58; P<.0001). The median radiographic progression-free survival was not reached with SHR3680 compared with 25.1 months for bicalutamide.
Overall survival data were not yet mature, but improved overall survival was observed with SHR3680 compared with bicalutamide (HR=0.58; 95% CI, 0.42-0.80; P=.0009).
The researchers also examined several secondary endpoints, all of which favored SHR3680. Specifically, the median time to PSA progression (P<.0001), time to next skeletal-related event (P=.0032), and the time to initiation of new anti-prostate cancer therapy (P<.0001) were all significantly improved with SHR3680 compared with bicalutamide.
The overall response rate was 81.0% for SHR3680 compared with 68.2% for bicalutamide (P=.0065).
The researchers noted that the frequency of adverse events of any cause or any grade were similar between the two study arms. Grade 3 or worse treatment-related adverse events occurred in 19.2% of patients assigned to SHR3680 and 13.9% of those assigned bicalutamide. No seizures occurred in the SHR3680 arm.
According to the researchers, a new drug application has been submitted for SHR3680 based on these data.