Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study
Author(s): Amar U. Kishan, MD1,2; Luca F. Valle, MD1,3; Holly Wilhalme, MS4; Carol Felix, BS1; Rejah Nabong, BS5; Jesus E. Juarez-Casillas, MS, BS1; Kevin Flores, BS1; T. Martin Ma, MD, PhD6; Vinicius Ludwig, MD5; Mariko Nakayama, MD5,7; Zachary Ells, BS5; Magnus Dahlbom, PhD5; Michael Lauria, PhD1; Catherine Meyer, PhD5; Minsong Cao, PhD8; Joanne B. Weidhaas, MD, PhD1; Donatello Telesca, PhD9; Kristen McGreevy, PhD9; Nicholas G. Nickols, MD, PhD1,3; Danielle Karasik, BS1; Sophia Parmisano, BS1; T. Vincent Basehart, BS1; Wayne Brisbane, MD2; Leonard Marks, MD2; Matthew B. Rettig, MD3,10; Robert E. Reiter, MD2; Paul C. Boutros, PhD2,11; Martin Allen-Auerbach, MD5; Johannes Czernin, MD5; Michael L. Steinberg, MD1; Jeremie Calais, MD, PhD5;
Source: DOI: 10.1200/JCO-25-01553
Dr. Maen Hussein's Thoughts
For our radiation oncology colleagues, the addition of PSMA-directed therapy prior to stereotactic body radiation therapy (SBRT) improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Two cycles of PSMA-directed therapy were administered before SBRT.
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 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 177Lu-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 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 177Lu + SBRT n = 45), with 87 evaluable patients (SBRT n = 42 and 177Lu + SBRT n = 45). a median follow-up of 22 months, the addition of 177Lu 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 177Lu + SBRT group). Prognostic biomarkers for PFS were identified.
CONCLUSION
Compared with SBRT alone, the addition of 177Lu-PNT2002 to SBRT significantly improved PFS in patients with orHSPC without an attendant increase in toxicity.
Author Affiliations
1Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA; 2Department of Urology, University of California, Los Angeles, Los Angeles, CA; 3Greater Los Angeles VA Medical Center, Los Angeles, CA; 4Department of Medicine Statistical Core, University of California, Los Angeles, Los Angeles, CA; 5Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA; 6Department of Radiation Oncology, University of Washington, Seattle, WA; 7Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA; 8Department of Radiation Oncology, University of San Francisco, San Francisco, CA; 9Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA; 10Department of Medicine, University of California, Los Angeles, Los Angeles, CA; 11Department of Human Genetics, University of California, Los Angeles, Los Angeles, CARelated Articles
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