What question did this study set out to answer?

This trial aims to compare the effectiveness of alpha-emitting 225 Ac-PSMA and beta-emitting 177 Lu-PSMA in improving progression-free survival for patients with oligorecurrent prostate cancer.

May 30, 2026

Alpha-emitting radionuclide or beta-emitting radionuclide combined with metastasis-directed stereotactic body radiotherapy for oligorecurrent prostate adenocarcinoma (ANDROMEDA): A phase II trial.

Key Points

This trial aims to compare the effectiveness of alpha-emitting 225 Ac-PSMA and beta-emitting 177 Lu-PSMA in improving progression-free survival for patients with oligorecurrent prostate cancer.
Phase II, non-blinded, single-center randomized trial with 96 patients (48 per treatment arm).
Participants were randomized to receive either 2 cycles of 177 Lu-PSMA or 1 cycle of 225 Ac-PSMA followed by stereotactic body radiotherapy.
Progression-free survival was defined by the emergence of new lesions or local progression based on PSMA-PET imaging.
The target PSA-based recurrence rate after 24 months for 177 Lu-PSMA is hypothesized to be ~50%, while for 225 Ac-PSMA it is expected to be ~30% (PFS HR~0.51).
A total accrual time of 1.5 years with a median follow-up time of 24 months is planned to assess outcomes.
Early stopping guidelines are in place for significant grade 4-5 toxicity, ensuring patient safety during the trial.

Abstract

TPS3175 Background: The recent LUNAR study (NCT05496959) found that adding beta-emitting 177 Lutetium-PNT2002 ( 177 Lu-PSMA) to stereotactic body radiation therapy (SBRT) more than doubled median progression-free survival (PFS) compared to SBRT alone in oligorecurrent hormone-sensitive prostate cancer (orHSPC), hazard ratio (HR)=0.37. However, the relative efficacy compared to novel alpha-emitting 225 Actinium-PSMA-617 ( 225 Ac-PSMA) is unknown. The hypothesis is that 225 Ac-PSMA will improve PFS by treating more micrometastases, given its higher radiobiologic effectiveness. We aim to compare the relative benefit of 2 cycles of 177 Lu-PSMA versus 1 cycle of 225 Ac-PSMA followed by SBRT metastasis-directed therapy (MDT). Methods: ANDROMEDA (NCT07150715) is a phase II, non-blinded, single-center randomized trial for individuals with orHSPC and 1-5 PSMA-avid metastases outside the prostate/prostate bed (N1 and/or M1). Eligibility criteria include testosterone >150 ng/dL, ≥18 years, and ECOG performance status ≤2. Exclusion criteria include de novo metastatic disease, castrate-resistance (testosterone 30% SUV increase or >20% increase in the sum of the longest lesion diameters) with a PSA rise. For those alive without progression, PFS will be censored at the time of the last scan. All randomized subjects will be analyzed based on intent-to-treat. Secondary endpoints include 24-month disease burden by PSMA-PET, physician-scored toxicity, patient-reported quality of life, ADT-free survival, local control of SBRT lesions at 24 months after last radionuclide infusion, and time-to-progression (locoregional, distant, new metastasis). We hypothesize that the 24-month post-SBRT PSA-based recurrence rate of 177 Lu-PSMA will be ~50%, which will be reduced with 225 Ac-PSMA to ~30% (PFS HR~0.51). We anticipate an accrual time of 1.5 years and a median follow-up time of 24-months. A sample size of 96 patients (48 per arm) would provide 80% power to detect the expected difference in PFS at a 0.1 alpha level. Assuming a 10% drop-out/screen failure rate, the target trial accrual is 107 patients. Early stopping guidelines include monitoring site-specific grade 4-5 toxicity with a safety threshold of 20% from the time of the first enrolled patient, which would trigger halting the trial and safety consultation. ANDROMEDA is currently open for enrollment. Clinical trial information: NCT07150715 .

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