Overview
New data presented at the American Society for Radiation Oncology (ASTRO) meeting suggest that adding the radiopharmaceutical Lu-177 PNT2002 to stereotactic body radiation therapy (SBRT) can significantly delay disease progression in men with oligometastatic, or limited, prostate cancer. The LUNAR trial compared SBRT alone to a two-cycle course of Lu-177 PNT2002 followed by SBRT, and the combination markedly extended progression-free survival (PFS) without increasing treatment-related toxicity.
The LUNAR Trial: Design and Population
The randomized study enrolled 92 men with oligometastatic prostate cancer—meaning cancer spread to one to five sites beyond the prostate after initial therapy. Participants were assigned to SBRT alone (n = 47) or Lu-177 PNT2002 administered in two cycles followed by SBRT (n = 45). The median follow-up was 22 months. Researchers were exploring whether PSMA-targeted radioligand therapy could tackle occult micrometastatic disease that eludes conventional imaging and treatment.
Key Findings
Among the primary endpoints, the addition of Lu-177 PNT2002 to SBRT nearly tripled progression-free survival. The combined treatment yielded a median PFS of 18 months versus seven months with SBRT alone (p < 0.001). In multivariable analyses that adjusted for PSA levels, prior hormonal therapy, and the number of lesions, the Lu-177 PNT2002–SBRT combination remained independently associated with improved PFS.
Striking secondary results also favored the combination. Hormone therapy could be delayed longer in the Lu-177 PNT2002 arm—24 months compared with 14 months for SBRT alone (p < 0.0001). PSA declines of 50% or greater were observed in 52% of patients receiving the combination, versus 31% in the SBRT-only group (p = 0.04). Importantly, there was no observed increase in severe toxicities with the radiopharmaceutical addition, suggesting the approach is tolerable for patients in this disease state.
Kishan noted that nearly all disease progression events (98%) were new metastases rather than regrowth at treated sites, a finding attributed to the trial’s use of highly sensitive PSMA-PET/CT imaging. He also cautioned that while the intervention performed well, 64% of patients in the study still experienced some progression, underscoring the need for optimization of dosing, cycles, and patient selection in future work.
How the Therapy Works
Lu-177 PNT2002 combines lutetium-177 with a PSMA-targeting ligand that binds to prostate cancer cells. This radioligand delivers targeted radiation to cancer cells, including micrometastatic disease that SBRT may not reach. When used in conjunction with SBRT—an ultras precise, high-dose form of radiation directed at visible lesions—the strategy aims to suppress occult spread while maintaining tolerable safety. PSMA-based radioligand therapy like Lu-177 PNT2002 is a growing area of research for extending disease control in advanced prostate cancer.
Clinical Implications
These results point to a potential new paradigm for managing oligometastatic prostate cancer. By introducing PSMA-targeted radioligand therapy before metastasis-directed SBRT, clinicians may be able to prolong the interval before systemic therapies become necessary. Delaying hormone therapy has meaningful quality-of-life and symptom-related implications for patients. However, the results are preliminary and derived from a single trial with a modest sample size; confirmation in larger, possibly multi-center studies with longer follow-up is essential to validate these benefits and to refine dosing regimens.
Safety and Tolerability
Across arms, treatment was generally well tolerated with no notable increase in severe adverse events caused by adding Lu-177 PNT2002. This favorable safety signal is encouraging, given the potential for systemic therapies to add toxicity. Nonetheless, careful monitoring for hematologic and organ toxicity remains important in early-phase radioligand therapy trials.
Limitations and Future Directions
As Kishan acknowledged, the high sensitivity of PSMA-PET imaging in this study may have contributed to the high rate of new metastases observed at progression. The relatively small, single-cohort design and the median follow-up of about two years call for cautious interpretation. Future work should explore optimal dosing, the number of cycles, patient selection criteria, and combination timing (e.g., which lesions to target first). Additional trials could assess long-term outcomes such as overall survival and quality of life, helping to define the role of Lu-177 PNT2002 in standard practice.
Conclusion
The LUNAR trial provides compelling early evidence that Lu-177 PNT2002, when given before SBRT, can substantially extend progression-free survival for men with oligometastatic prostate cancer without adding toxicity. While promising, these findings require validation in larger populations and longer follow-up before changing universal practice. If confirmed, this approach could represent a meaningful advance in delaying systemic therapy and improving disease control for patients facing limited metastatic prostate cancer.
