(UroToday.com) The 2022 EAU annual meeting featured a game changing session, including a presentation by Dr. Steven Joniau discussing the results of ARNEO, a randomized phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for high-risk prostate cancer. Dr. Joniau notes that according to recent SEER data, treatment for high- and very-high-risk prostate cancer remains a clinically unmet need. The incidence of high- and very-high-risk prostate cancer is ~20%, with 5- and 10-year prostate cancer-specific mortality rates of ~75% and 65%, respectively.
Multiple trials have investigated the role of neoadjuvant hormonal therapy prior to radical prostatectomy, with most suggesting benefit in terms of pathological response, but with no benefit in terms of survival. However, these trials were based on first-generation anti-androgens or LHRH agonists, were not powered to detect survival differences, and were mainly among men with low and intermediate-risk prostate cancer.
The ARNEO trial recruited high risk (cT3-T4, PSA > 20 ng/mL, Gleason score 8-10, cN1, 2-3 intermediate risk factors) M0 men who subsequently received a blinded PSMA PET/MRI and were randomized 1:1 to 3 months of degarelix + apalutamide versus 3 months of degarelix + placebo. Patients then underwent repeat blinded PSMA PET/MRI followed by radical prostatectomy. The primary endpoint for this trial was the difference in percentage of minimal residual disease (<0.25 mL) and secondary endpoints included: PSA kinetics, toxicity, quality of life, and biomarkers for pathological response such as PSMA PET/MRI and immunohistochemistry (ERG, PTEN, PSMA, Ki67, p53) on diagnostic biopsies:
There were 45 patients randomized to the degarelix + apalutamide arm and 44 patients randomized to the degarelix + placebo arm. The baseline characteristics for each arm were well-balanced and are as follows:
The primary endpoint of minimal residual disease (< 0.25 mL) was 38% in the apalutamide arm versus 9% in the placebo arm (p = 0.002), with a residual burden of disease of 0.48 mL for the apalutamide arm and 1.7 mL for the placebo arm (p < 0.001):
Additionally, downstaging to pT2 disease was significantly more frequent in the apalutamide arm (51% vs 27%, p = 0.03). Both PSMA PET/CT estimated volume and PSMA PET SUVmax (intensity) correlated with cancer volume at final pathology:
Finally, patients that had PTEN loss at diagnostic biopsy were less likely to achieve minimal residual disease (11% versus 43%, p = 0.002).
Dr. Joniau concluded his presentation discussing the results of ARNEO, a randomized phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for high-risk prostate cancer with the following concluding points:
- Patients treated with degarelix + apalutamide achieved a significantly better tumor response compared to patients treated with degarelix plus a matched placebo
- PSMA PET/CT estimated volume and PSMA PET SUVmax after neoadjuvant therapy predict pathological response
- PTEN loss is a negative predictor of minimal residual disease
- These results provide a solid basis for future planning/running phase 3 clinical trials
Presented by: Steven Joniau, MD, PhD, Department of Urology, University Hospitals Leuven, Leuven, Belgium
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.
Related Content: EAU 2022: Discussion: ARNEO - A Randomized Phase II Trial Of Neoadjuvant Degarelix With Or Without Apalutamide Prior To Radical Prostatectomy For High-Risk Prostate Cancer