Alpha-emitting radionuclide or beta-emitting radionuclide combined with metastasis-directed stereotactic body radiotherapy for oligorecurrent prostate adenocarcinoma (ANDROMEDA): A phase II 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 <50 ng/mL with rising PSA), ADT/chemotherapy within 6 months of enrollment, and neuroendocrine histology. Participants are randomized 1:1 to 2 cycles 177 Lu-PSMA (7.4 GBq/cycle, 6 weeks apart) or 1 cycle of 225 Ac-PSMA (8 MBq, once), followed by SBRT to all lesions 1-2 weeks after radioligand therapy infusion. The primary endpoint of PFS is defined as the time from randomization to either 1) a new PSMA-avid lesion or 2) PSMA-PET local progression (>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 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (16)
Kekoa Taparra
Carol Felix
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Sophia Parmisano
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Holly Wilhalme
Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA
Rejah Nabong
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Stephanie Lira
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Matthew Rettig
Department of Medical Oncology, University of Southern California, Los Angeles, Los Angeles, CA
Robert Evan Reiter
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Adam E. Singer
Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Joanne B. Weidhaas
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Johannes Czernin
Ahmanson Translational Theranostics Division, University of California, Los Angeles, Los Angeles, CA
Martin S. Allen-Auerbach
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Luca Faustino Valle
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Michael L. Steinberg
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Jeremie Calais
Luca F. Valle, MD, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, Radiation Oncology Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, Jeremie Calais, MD, PhD, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, Department of Nuclear Medicine, University of California Los Angeles, Los Angeles, CA, Amar U. Kishan, MD, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA
Amar Upadhyaya Kishan
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA