Treatment with lutetium-177 (Lu-177) PNT2002 before stereotactic body radiation therapy (SBRT) continues to improve outcomes in men with advanced prostate cancer, according to a recently updated clinical trial.
A group from the University of California, Los Angeles, updated an analysis of outcomes from the LUNAR trial by 10 months, with findings suggesting the benefits of combining radioligand therapy with SBRT extend to more clinically meaningful disease states, noted lead author Amar Kishan, MD, and colleagues.
“We found that the combination of these treatments continued to show a progression-free survival and hormone therapy-free survival benefit,” the group wrote. The study was published October 12 in European Urology.
Findings from the original LUNAR trial report showed a significant progression-free survival (PFS) benefit in participants at a median follow-up of 22 months, with outcomes driven largely by new lesions detected on prostate-specific membrane antigen (PSMA) PET/CT scans, the authors noted. The trial protocol prespecified secondary and exploratory endpoints to capture longer-term, more clinically meaningful outcomes, they added.
For the study, 92 patients with PSMA-PET/CT-detected oligorecurrent hormone-sensitive prostate cancer (orHSPC) and one to five metastatic lesions were randomized 1:1 to SBRT alone or two cycles of neoadjuvant Lu-177 PNT2002 followed by SBRT. Secondary endpoints included hormonal therapy-free survival and 24-month progression-free status; exploratory endpoints included polymetastatic PFS, castration-resistant disease-free survival (CRFS), and conventional imaging-based PFS (CT-PFS).
At a median follow-up of 31.9 months, Lu-177 PNT2002 significantly extended median PFS from 7.4 months to 17.6 months, with 33% of patients in the combination group showing no evidence of disease at 24 months compared with 12% in the SBRT-alone group. Hormonal therapy-free survival was also significantly improved. In secondary results, exploratory analyses demonstrated improvements in polymetastatic PFS and CRFS. CT-PFS trended toward improvement without reaching statistical significance, and no new safety signals were observed, the group reported.
“This updated analysis of a randomized phase II trial demonstrated that the addition of two cycles of Lu-177 PNT2002 to SBRT in patients with orHSPC improved multiple end points, including polymetastatic PFS, time to castration-resistant disease, and CT-PFS,” the authors wrote.
The authors noted that not all patients with oligorecurrent prostate cancer may require systemic intensification alongside SBRT, and that PSMA-PET/CT scans will play a critical role in identifying which patients benefit most in future studies. They also wrote that it is too early to evaluate overall survival differences, with the LUNAR trial scheduled to follow patients for up to 60 months, with primary completion estimated in September 2032.
Ultimately, substantially more data on the long-term durability of the benefits of neoadjuvant Lu-177 PNT2002 followed by SBRT are still to come, the authors suggested.
“Further studies will indicate whether the outcomes can be replicated and/or improved upon,” the authors concluded.
The full study is available here.
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