<sup>177</sup> Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study
Abstract
PURPOSE Progression after metastasis-directed therapy via stereotactic body radiotherapy (SBRT) for oligorecurrent hormone-sensitive prostate cancer (orHSPC) is common. We aimed to assess whether the addition of neoadjuvant prostate-specific membrane antigen (PSMA)–targeting radioligand therapy to SBRT would improve outcomes. METHODS The LUNAR trial was a single-center, randomized, open-label, controlled phase II trial conducted at the University of California, Los Angeles. Eligible participants had orHSPC as determined by the presence of one to five lesions identified on PSMA positron emission tomography/computed tomography (PET/CT). After stratifying by stage (N1/M1a v M1b) and lesion count (1 v 2-3 v 4-5), we randomly assigned patients 1:1 to receive SBRT to all lesions or two cycles of 177 Lu-PNT2002 (6.8 GBq/cycle, 2 weeks apart) followed by SBRT to all lesions. The primary end point was progression-free survival (PFS), defined by PSMA PET/CT, salvage hormonal therapy, or death. PSMA PET/CT was acquired systematically at prostate-specific antigen progression and/or 12 months after SBRT. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov (identifier: NCT05496959 ). RESULTS From September 2, 2022, to November 9, 2023, 92 patients were randomly assigned (SBRT n = 47 and 177 Lu + SBRT n = 45), with 87 evaluable patients (SBRT n = 42 and 177 Lu + SBRT n = 45). At a median follow-up of 22 months, the addition of 177 Lu to SBRT significantly improved PFS (17.6 months [95% CI 15 months to not reached] v 7.4 months [95% CI, 6.0 to 13.5 months]; hazard ratio, 0.37 [95% CI, 0.22 to 0.61], P < .0001). The only grade 3 adverse events were lymphopenia (two patients [4.8%] in the SBRT group and three patients [6.7%] in the 177 Lu + SBRT group). Prognostic biomarkers for PFS were identified. CONCLUSION Compared with SBRT alone, the addition of 177 Lu-PNT2002 to SBRT significantly improved PFS in patients with orHSPC without an attendant increase in toxicity.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (31)
Amar U. Kishan
Luca F. Valle
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
Holly Wilhalme
Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA
Carol Felix
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Rejah Nabong
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Jesus E. Juarez-Casillas
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA
Kevin Flores
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA
T. Martin Ma
Department of Radiation Oncology, University of Washington, Seattle, WA
Vinicius Ludwig
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Mariko Nakayama
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Zachary Ells
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Magnus Dahlbom
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Michael Lauria
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA
Catherine Meyer
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Minsong Cao
Department of Radiation Oncology, University of San Francisco, San Francisco, CA
Joanne B. Weidhaas
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Donatello Telesca
Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA
Kristen McGreevy
Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA
Nicholas G. Nickols
Danielle Karasik
Department of Radiation Oncology, 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
T. Vincent Basehart
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA
Wayne Brisbane
Department of Urology, University of California, Los Angeles, Los Angeles, CA
Leonard Marks
Department of Urology, University of California, Los Angeles, Los Angeles, CA
Matthew B. Rettig
Robert E. Reiter
Department of Urology, University of California, Los Angeles, Los Angeles, CA
Paul C. Boutros
Martin Allen-Auerbach
Johannes Czernin
Ahmanson Translational Theranostics Division, 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