Treatment with lutetium-177 (Lu-177) PNT2002 before stereotactic body radiation therapy (SBRT) significantly improves outcomes for patients with advanced prostate cancer, according to research presented at the American Society for Radiation Oncology (ASTRO) meeting.
In a trial that tested the approach compared to SBRT alone, the addition of Lu-177 PNT2002 more than doubled progression-free survival (PFS) for patients, noted Amar Kishan, MD, of the University of California, Los Angeles.
“Adding two cycles of lutetium-177 PNT2002 to SBRT significantly improves PFS in men with oligorecurrent prostate cancer, presumably by action on occult metastatic disease without an increase in toxicity,” Kishan said, in a September 29 media briefing held by ASTRO.
SBRT itself – where oncologists deliver a precise, high-dose form of radiation therapy to tumors – is an emerging technique that has been shown to achieve longer-lasting cancer control than systemic therapies alone, Kishan said. Yet for most patients, the cancer ultimately returns, likely due to microscopic disease that scans cannot detect, he added.
Prostate-specific membrane antigen (PSMA)-based radioligand agents such as Lu-177 PNT2002 that combine lutetium-177 with ligands that bind to PSMA on cancer cells also show promise for improving progression-free survival in men with advanced cancers.
“The hypothesis we tested in the LUNAR trial is whether adding PSMA-based radioligand therapy with lutetium-177-PNT2002 to metastasis-directed SBRT would actually improve PFS in men with oligo recurrent prostate cancer by delaying occult micrometastatic disease,” Kishan said.
The researchers enrolled 92 patients with oligometastatic prostate cancer, a state of limited metastatic disease where the cancer grows in one to five sites outside the prostate region after initial therapy. Participants received either SBRT alone (n = 47) or two cycles of Lu-177 PNT2002 followed by SBRT (n = 45). The researchers followed participants for a median of 22 months.
According to the findings, patients had a PFS of 18 months with the combined treatment compared to seven months with SBRT alone (p < 0.001). On multivariable analysis adjusted for PSA, prior hormonal therapy and number of lesions, the addition of Lu-177 PNT2002 remained significantly associated with improved progression-free survival.
In addition, patients who received the Lu-177 PNT2002 before SBRT were able to delay hormone therapy by 24 months compared to 14 months with SBRT alone (p < 0.0001). PSA declines of 50% or greater were seen in 52% of patients on the combination arm, compared to 31% on the SBRT arm (p = 0.04). Both groups tolerated treatment well, and there was no increase in severe side effects with the addition of the radiopharmaceutical.
Lastly, Kishan noted that nearly all instances of disease progression (98%) were new metastases rather than regrowth at previously treated sites and that there were more progression events than the researchers expected. This was likely due to the trial’s use of highly sensitive PSMA-PET/CT imaging, he said.
“Ultimately, while this intervention worked well, 64% of patients even on the investigation alarm still had some progression, so we could further optimize the dose and cycle and other variables for these patients,” Kishan concluded.
