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, MD^1,2; Luca F. Valle, MD^1,3; 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, MD^5,7; 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, PhD^1,3; Danielle Karasik, BS¹; Sophia Parmisano, BS¹; T. Vincent Basehart, BS¹; Wayne Brisbane, MD²; Leonard Marks, MD²; Matthew B. Rettig, MD^3,10; Robert E. Reiter, MD²; Paul C. Boutros, PhD^2,11; 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, CA

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