UPDATE: LUNAR Trial Follow-Up Strengthens Case for Earlier PSMA Radioligand Therapy

Longer follow-up from the randomized phase 2 LUNAR trial suggests that PSMA-targeted radioligand therapy may do more than simply delay progression when used early in men with oligorecurrent hormone-sensitive prostate cancer.
LUNAR enrolled 92 men whose prostate cancer had returned after previous treatment, with one to five metastases visible on PSMA PET/CT. Importantly, patients were not receiving continuous androgen deprivation therapy (no ADT). They were randomized to stereotactic body radiotherapy (SBRT) alone or two cycles of 177Lu-PNT2002 followed by SBRT.

The original analysis (which we discussed in this previous post one year ago) had already shown a large improvement in progression-free survival. At 22 months of follow-up, median PFS was 17.6 months with 177Lu-PNT2002 plus SBRT versus 7.4 months with SBRT alone, corresponding to a 63% reduction in the risk of progression. PSA50 responses were also more frequent with the combination, occurring in 52% versus 31% of patients.
The new analysis extends median follow-up to 31.9 months and suggests that this benefit may translate into more meaningful changes in the pattern of disease progression. The risk of progression or starting additional hormonal therapy remained 62% lower with the radioligand combination. At two years, 33% of patients receiving 177Lu-PNT2002 plus SBRT had no detectable disease, compared with 12% receiving SBRT alone.
More interestingly, only 3 patients in the combination arm developed widespread progression involving more than five new sites, compared with 9 patients treated with SBRT alone. Castration-resistant prostate cancer developed in 1 versus 7 patients, respectively. These analyses involve very small numbers and were exploratory, but they raise the possibility that treating microscopic PSMA-positive disease early could alter the later course of the cancer rather than merely postpone the next visible recurrence.
The biological rationale is particularly attractive in oligorecurrent disease. SBRT can eliminate the lesions visible on imaging, but even modern PSMA PET cannot detect every microscopic deposit. A systemic radioligand such as 177Lu-PNT2002 can circulate throughout the body and potentially target those invisible PSMA-expressing cells before they become established metastases.
No new safety concerns appeared with longer follow-up, and serious treatment-related toxicity remained uncommon.

Source.