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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)

  • Ding-Wei Ye,
  • Weijie Gu,
  • Weiqing Han,
  • Hong Luo,
  • Fangjian Zhou,
  • Dalin He,
  • Lulin Ma,
  • Hongqian Guo,
  • Chaozhao Liang,
  • Tie Chong,
  • Jun Jiang,
  • Zhiwen Chen,
  • Yong Wang,
  • Qing Zou,
  • Ye Tian,
  • Jun Xiao,
  • Jian Huang,
  • Xinfeng Yang,
  • Junliang Li,
  • Chunlei Jin

Background

Both TITAN and ARCHES studies have demonstrated significant clinical benefits of second-generation androgen receptor inhibitors (ARIs) plus ADT versus placebo plus ADT in the treatment of mHSPC. However, first-generation ARIs plus ADT is also widely used in clinic and how superior second-generation ARIs is to first-generation ones remains to be determined. Here, we evaluated the efficacy and safety of SHR3680, a novel oral ARI, versus bicalutamide (Bica) in high-volume mHSPC.

Methods

CHART is a randomized, open-label, phase 3 study (NCT03520478). Patients (pts) with mHSPC were randomized 1:1 to ADT plus either SHR3680 (240 mg/d) or Bica (50 mg/d). All pts had high-volume disease adapted from the CHAARTED study. The primary endpoints were radiographic progression-free survival (rPFS) assessed by independent review committee (IRC) and overall survival (OS). As of May 16, 2021, 209 rPFS events per IRC and 153 deaths occurred and a preplanned interim analysis for rPFS was done.

Results

654 pts were randomized to receive SHR3680 (n = 326) or Bica (n = 328). At data cutoff, the median follow-up duration was 22.1 mo in SHR3680 group and 20.4 mo in Bica group. SHR3680 significantly reduced the risk of radiographic progression or death than Bica (HR, 0.44; 95% CI, 0.33-0.58; p < 0.0001; median, not reached vs 25.1 mo). OS data were immature but an improved OS was observed in SHR3680 group compared to Bica group (HR, 0.58; 95% CI, 0.42-0.80; p = 0.0009). All secondary efficacy endpoints favored SHR3680 plus ADT (Table). Frequencies of adverse events of any cause in any grade were similar between groups. Grade ≥3 treatment-related adverse events occurred in 19.2% and 13.9% of pts in SHR3680 and Bica groups, respectively. No seizure occurred in SHR3680 group.

Conclusions

SHR3680 plus ADT significantly improved rPFS versus Bica plus ADT in pts with high-volume mHSPC, with a desirable safety profile. New drug application has been submitted to seek approval based on the data presented here. Clinical trial information: NCT03520478.