OPTIMAS: A phase II randomized, decentralized, de-escalation trial in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) achieving optimal PSA response.

Abstract

TPS288 Background: An optimal PSA response, defined as ≤0.2 ng/mL is achieved by ~51% of pts with mHSPC at 6–8 months after treatment (Rx) with androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) +/- docetaxel and is associated with a 61% reduction in risk of death (HR 0.39, 95% CI 0.30–0.50; Naqvi SAA ASCO GU 2023). Pts receiving continuous ADT experience numerous adverse effects including fatigue, loss of bone density, muscle loss, weight gain, gynecomastia, hot flashes, sexual dysfunction, increased cardiovascular risk and skeletal-related events. Since achieving optimal PSA response is prognostic of prolonged overall survival, these pts may be candidates for a de-intensified Rx strategy which may result in better quality of life. To investigate this, we initiated a de-intenstification trial in pts with mHSPC. Methods: This IRB approved, investigator-initiated, single-center, multi-cohort, phase 2, randomized, open-label study will enroll 160 pts. Cohort A will enroll 100 pts (step 1) with mHSPC who haven’t initiated systemic Rx for metastatic disease and will be treated with relugolix (R)+ARPI +/-standard of care Rx. Pts achieving PSA ≤0.2 ng/mL will be randomized (step 2) 1:1 to intermittent or continuous R+ARPI. Primary objective: To assess difference in fatigue at 6 months after randomization between intermittent vs continuous arms. In a prior study, pts with mHSPC who received ADT+ARPI had a mean baseline brief fatigue inventory worst fatigue (BFI3) score of 2.04 with a standard deviation (SD) of 2.176, and the SD was similar in control group. Null hypothesis: there is no difference in mean BFI3 in the control arm (continuous Rx) and experimental arm (intermittent Rx) 6 months after randomization. Alternative hypothesis: difference is ≥ 2 points. 52 pts (26 in each arm) are required to have 90% power at one-side 2.5% significance level, using two-sample t-test assuming equal variance. With 100 pts enrolled in Step 1 and expected 60% pts reaching PSA ≤0.2 ng/ml, 58 evaluable pts will be randomized at Step 2 to achieve 52 pts for primary analysis (assumed dropout rate 10%). Cohort B will enroll 60 pts with mHSPC who initiated ADT Rx for metastatic disease and achieved PSA ≤0.2 ng/ml. Pts will receive intermittent R+ARPI. Primary objective: To assess progression-free survival (PFS) on intermittent R+ARPI at 1 year. Assuming 1-year PFS rate of 92%, per Clopper-Pearson exact method with 60 pts, achieving expected 92% PFS rate provides 95% confidence that the true PFS rate is no lower than 83.3%. Secondary objectives for cohort A & B: To evaluate Rx effects on patient-reported outcomes (PROs) and efficacy of intermittent R+ARPI. Exploratory objectives: ecological momentary assessments, safety, PRO association with testosterone, tissue and blood biomarker assessment. Clinical trial information: NCT07216248 .