177Lu-PSMA-617 Consolidation Therapy After Docetaxel in Patients with Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer: A Randomized, Phase 2 Trial

177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617) has shown positive survival outcomes in metastatic castration-resistant prostate cancer. However, there are limited data in the hormone-sensitive setting. Here, in the CONSOLIDATE trial (177Lu-PSMA-617 Consolidation Therapy After Docetaxel in Patients with Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer), we intended to evaluate the role of 177Lu-PSMA-617 as consolidation therapy for residual disease after chemohormonal treatment in patients with synchronous high-volume metastatic hormone-sensitive prostate cancer (mHSPC). Methods: This was an investigator-initiated randomized, parallel-group, open-label phase 2 trial. Synchronous high-volume mHSPC patients treated with androgen-deprivation therapy plus docetaxel and having residual nonprogressive disease after docetaxel completion (defined as prostate-specific antigen [PSA] > 0.2 ng/mL with PSMA-positive disease on 68Ga-PSMA-11 PET/CT) were randomized in a 1:1 ratio to the experimental arm (177Lu-PSMA-617, 7.4 GBq/cycle × 2, 6 wk apart with protocol-permitted standard of care) or control arm (protocol-permitted standard of care alone). The primary endpoint was the proportion of patients achieving a PSA level of 0.2 ng/mL or less at 6 mo from randomization. Secondary endpoints included objective radiographic response rate, radiographic progression-free survival (PFS), PSA PFS, and toxicities. Results: The trial was terminated early because of poor accrual after the coronavirus disease pandemic and a change in treatment guidelines for mHSPC. Thirty high-volume mHSPC patients were randomized between January 2021 and June 2024. The primary endpoint was achieved in 9 of 15 (60%; 95% CI, 35%-85%) patients in the experimental arm versus 2 of 15 (13%; 95% CI, 0%-30%) in the control arm (risk ratio, 4.5; 95% CI, 1.2-17.4; P = 0.008). The objective radiographic response rates were 8 of 15 (53%; 95% CI, 28%-78%) and 1 of 15 (7%; 95% CI, 0%-19%) in the experimental and control arms, respectively (P = 0.014). The estimated median radiographic PFS and PSA PFS were 18 mo (95% CI, 9-27 mo) and 15 mo (95% CI, 12-18 mo), respectively, in the experimental arm versus 9 mo (95% CI, 4-14 mo) and 9 mo (95% CI, 1-17 mo), respectively, in the control arm. No grade 3 or 4 toxicity was noted with the addition of 177Lu-PSMA-617 in the experimental arm. Conclusion: In synchronous high-volume mHSPC patients having residual disease after chemohormonal treatment, 177Lu-PSMA-617 consolidation therapy demonstrated promising efficacy and safety outcomes. Larger phase 3 trials are warranted to definitively establish its survival benefit.