Combined with androgen deprivation therapy (ADT), novel oral androgen receptor inhibitor, SHR3680, significantly improved radiographic progression free survival (rPFS) in patients with high-volume, metastatic, hormone–sensitive prostate cancer compared to bicalutamide, according to results from an interim analysis of the phase 3 CHART trial presented at 2022 ASCO Annual Meeting.

“Both TITAN and ARCHES studies have demonstrated significant clinical benefits of second-generation androgen receptor inhibitors plus ADT versus placebo plus ADT in the treatment of [metastatic hormone–sensitive prostate cancer],” wrote Ding-Wei Ye, MD, Fudan University Shanghai Cancer Center, China, and colleagues.

“However, first-generation [androgen receptor inhibitors] plus ADT is also widely used in clinic and how superior second-generation [androgen receptor inhibitors] is to first-generation ones remains to be determined,” they continued.

The CHART trial randomized 654 patients in a 1:1 ratio to receive ADT plus either SHR3680 (n = 326) or bicalutamide (n = 328). The primary end points were rPFS and overall survival (OS).

After 209 rPFS events and 153 deaths as of May 16, 2021, this preplanned interim analysis of rPFS was done. At the time of data cut-off, the median follow-up duration was 22.1 months in the SHR3680 group and 20.4 months in the bicalutamide group.

There was a significant reduction of risk of radiographic progression or death with SHR3680 compared to bicalutamide, with median rPFS of not reached vs 25.1 months, respectively (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.33 to 0.58; P <.0001). While OS data was immature, researchers observed an improved OS in the SHR3680 group compared to bicalutamide (HR, 0.58; 95% CI, 0.42 to 0.80; P = .0009).

Secondary efficacy end points (time to prostate-specific antigen (PSA) progression, time to next skeletal-related event, time to initiation of new anti-prostate cancer therapy, objective response rate, PSA undetectable rate) all favored SHR3680.

In terms of safety, the frequency of adverse events of any case in any grade were similar between the groups. Grade ≥3 treatment-related adverse events occurred in 19.2% of patients in the SHR3680 group and 13.9% in the bicalutamide group. There was no occurrence of seizures in the SHR3680 group.

“SHR3680 plus ADT significantly improved rPFS versus [bicalutamide] plus ADT in patients with high-volume [metastatic hormone–sensitive prostate cancer], with a desirable safety profile,” wrote Dr Ye and colleagues.

“New drug application has been submitted to seek approval based on the data presented here,” they concluded.

Source:

Ye DW, Gu W, Han W, et al. A phase 3 trial of SHR3680 versus bicalutamide in combination with androgen deprivation therapy (ADT) in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC). Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL. Abstract 5005.