Adding the targeted radioactive drug 177Lu-PNT2002 with stereotactic body radiation therapy, or SBRT, may help keep recurrent prostate cancer under control longer than SBRT alone, according to new research led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center. The team found patients who received the combination were less likely to develop widespread disease or hormone-resistant cancer, suggesting the treatment may offer benefits beyond delaying the initial return of the disease.
The findings, published in the journal European Urology, come from an updated analysis of the phase 2 LUNAR trial, which followed men for nearly three years after their prostate cancer had returned and was detected in a limited number of sites.
“Our earlier findings showed that adding 177Lu-PNT2002 could significantly delay progression and the need for hormone therapy,” said Dr. Amar Kishan, executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA and first author of the study. “But with longer follow-up, we're seeing signs that the benefit may extend beyond simply delaying recurrence, including a potential reduction in the risk of widespread disease and cancer that no longer responds to hormone therapy. These findings suggest we may be able to treat cancer cells that are present elsewhere in the body but are too small to detect, while giving patients more time before they need hormone therapy.”
Why this matters
For some men with prostate cancer, the disease returns after initial treatment and can be detected in only a few locations. Doctors can use SBRT to target and destroy those visible tumors. But cancer cells may also be present elsewhere in the body at levels too small to be detected even by highly sensitive PSMA PET scans.
Because 177Lu-PNT2002 travels through the bloodstream and targets PSMA, a protein found on most prostate cancer cells, the treatment may be able to reach some of this otherwise undetectable disease.
The approach could be particularly important for patients who want to delay hormone therapy. Although hormone therapy can control recurrent prostate cancer, long-term treatment can cause side effects and affect quality of life.
What the study did
The LUNAR trial included 92 men with oligorecurrent hormone-sensitive prostate cancer, meaning their cancer had returned and spread to one to five sites that could be identified on PSMA PET/CT and treated with SBRT.
The patients were randomly assigned to receive either SBRT alone or two cycles of 177Lu-PNT2002 followed by SBRT. The radioactive treatment was given about eight weeks apart, with SBRT administered after the second cycle.
The researchers followed the patients for a median of 31.9 months. They evaluated progression-free survival, as well as several additional measures of how the cancer progressed, including whether patients developed more widespread disease, castration-resistant prostate cancer or progression on conventional imaging.
What they found
The longer follow-up continued to show a benefit from adding 177Lu-PNT2002 to SBRT. The risk of progression or needing additional hormone therapy was 62% lower in the combination group than in the SBRT-alone group.
At 24 months, 33% of patients who received 177Lu-PNT2002 followed by SBRT had no detectable disease, compared with 12% of those who received SBRT alone.
The researchers also found fewer patients in the combination group developed widespread disease. Three patients receiving 177Lu-PNT2002 and SBRT developed more than five new cancer sites, compared with nine patients who received SBRT alone.
Similarly, one patient in the combination group developed castration-resistant prostate cancer, compared with seven patients in the SBRT-alone group. Because these were exploratory analyses with relatively few events, the findings will need to be confirmed in larger studies.
The combination also showed a trend toward longer control of disease on conventional imaging, which is used to detect larger or more established tumors.
In the earlier analysis of the trial, patients who received 177Lu-PNT2002 followed by SBRT went a median of 17.6 months without progression or the need for additional hormone therapy, compared with 7.4 months for those who received SBRT alone.
The researchers observed no new safety signals with longer follow-up and serious treatment-related side effects remained uncommon.
What this means for patients
For patients whose prostate cancer has returned in only a few places, the goal of treatment is often to control the visible tumors while delaying the need for hormone therapy and preventing the cancer from spreading more widely.
The findings suggest that combining a treatment that targets visible tumors with a radioactive drug that travels throughout the body may offer a way to address both visible and microscopic disease.
“This is an important step toward understanding whether we can use these treatments earlier, when the amount of cancer in the body is still relatively small,” Kishan said.
The researchers say the findings support further study of PSMA-targeted radioligand therapy earlier in the course of prostate cancer, before patients develop more advanced or treatment-resistant disease.
About the researchers
The study’s senior author is Jeremie Calais. Other UCLA authors are Holly Wilhalme, Carol Felix, Johanna Enke, Farzana Ali, Rejah Nabong, Jesus Juarez Casillas, Kevin Flores, Vinicius Ludwig, Mariko Nakayama, Zachary Ells, Magnus Dahlbom, Michael Lauria, Catherine Meyer, Joanne Weidhaas, Donatello Telesca, Kristen McGreevy, Nicholas Nickols, Sophia Parmisano, Wayne Brisbane, Leonard Marks, Adam Singer, Matthew Rettig, Robert Reiter, Luca Valle, Martin Allen-Auerbach, Johannes Czernin and Michael Steinberg.
The study was funded by Lantheus.
