KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the impact of neoadjuvant darolutamide combined with ADT in patients with HRLPC/VHRLPC undergoing RP.
- The primary endpoint was to determine PRR and MRD.
- Researchers noticed that neoadjuvant darolutamide plus ADT demonstrated improved clinical and pathological responses in men with HRLPC/VHRLPC.
Radical prostatectomy (RP) poses challenges with adverse surgical outcomes and heightened disease progression risks in high-risk/very high-risk localized prostate cancer (HRLPC/VHRLPC) patients. Junlong Zhuang and his team aimed to assess neoadjuvant darolutamide, a next-gen androgen receptor inhibitor, combined with androgen deprivation therapy (ADT) for RP in HRLPC/VHRLPC patients.
Researchers performed an inclusive analysis in a multicenter, single-arm phase II clinical trial involving patients aged 18-75 with HRLPC/VHRLPC, defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA ≥ 20 ng/mL. VHRLPC criteria included cT3b-cT4, primary Gleason pattern 5, 2 or 3 high-risk features, and > 4 cores with Grade Group 4 or 5. Eligible patients underwent a 6-month regimen of neoadjuvant darolutamide plus ADT followed by RP.
The primary endpoint assessed was the pathological response rate, encompassing patients with pathologic complete response (pCR) or minimal residual disease (MRD). Secondary endpoints included safety, PSA progression-free survival (PFS), positive surgical margins rate, downstaging rate, and PSA response rate.
About 30 patients, all undergoing robotic-assisted RP, were enrolled. Median age was 71.0 years (IQR, 65.2-73.0), baseline PSA level was 37.8 ng/mL (IQR, 21.0-94.7). Predominantly, 93.3% had very high-risk localized prostate cancer (VHRLPC); 6.7% had HRLPC with 26.7% N1 disease, 86.7% cT3-4, 90% Gleason 8-10, and 77% PSA ≥ 20 ng/mL. Median prostate volume pre-RP was 19.4 mL (IQR, 15.6-28.4). Post-RP, 27 patients (90%) had undetectable PSA levels (<0.01 ng/mL). Pathological response rate was 40.0%, with 6.7% pCR and 33.3% MRD rates. Downstaging was achieved in 20 patients (66.7%), and positive surgical margins occurred in only 13.3%. The extracapsular extension was noted in 11 patients (36.6%) of cases.
The study concluded that preoperative administration of darolutamide plus ADT for 6 months significantly enhanced clinical and pathological responses in men with HRLPC/VHRLPC. Furthermore, the intervention demonstrated a favorable safety profile.
The study is sponsored by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Source: https://meetings.asco.org/abstracts-presentations/230315
Clinical Trial: https://clinicaltrials.gov/study/NCT05249712
Zhuang J, Wang Y, Zhang S, et al. (2024). “Neoadjuvant darolutamide plus androgen deprivation therapy for high-risk/very high-risk localized prostate cancer: A multicenter, open-labeled, single-arm phase II trial.” Presented at ASCO-GU 2024 (Abstract 321).
