In a single-center phase II trial (LUNAR) reported in the Journal of Clinical Oncology, Kishan et al found that the addition of neoadjuvant prostate-specific membrane antigen (PSMA)-targeting radioligand therapy with lutetium-177–labeled PNT2002 (LuPSMA PNT2002) to stereotactic body radiotherapy (SBRT) improved progression-free survival in patients with hormone-sensitive oligorecurrent prostate cancer.
Study Details
In the open-label trial, 87 evaluable patients with one to five lesions treated at the University of California, Los Angeles, were randomly assigned between September 2022 and November 2023 to receive SBRT to all lesions (n = 47) or two cycles of LuPSMA PNT2002 (6.8 GBq/cycle, 2 weeks apart) plus SBRT to all lesions (n = 45). SBRT was delivered in one, three, or five fractions of 16 to 18, 9 to 12, or 6 to 8 Gy. The primary outcome measure was progression-free survival (defined by PSMA positron-emission tomography/computed tomography findings, receipt of salvage hormonal therapy, or death).
Key Findings
Median follow-up was 22 months (interquartile range = 19–26 months). Median progression-free survival was 17.6 months (95% confidence interval [CI] = 15 months to not reached) in the LuPSMA PNT2002 plus SBRT group vs 7.4 months (95% CI = 6.0–13.5 months) in the SBRT group (hazard ratio = 0.37, 95% CI = 0.22–0.61, P < .0001).
A prostate-specific antigen decline of ≥ 50% was observed in 52% of the LuPSMA PNT2002 plus SBRT group vs 31% of the SBRT group (P = .04).
The only grade 3 adverse events observed (no grade 4 or 5 events) were lymphopenia, occurring in three patients (6.7%) in the LuPSMA PNT2002 plus SBRT group and two patients (4.8%) in the SBRT group. Grade 2 lymphopenia was observed in 17.8% vs 9.5% of patients. Other grade 2 events consisted of neutropenia in one patient, fatigue in two, and constipation in one in the LuPSMA PNT2002 plus SBRT group; and renal failure, nausea, and abdominal pain in one patient each in the SBRT group.
The investigators concluded: “Compared with SBRT alone, the addition of [LuPSMA PNT2002] to SBRT significantly improved [progression-free survival] in patients with [oligorecurrent hormone-sensitive prostate cancer] without an attendant increase in toxicity.”
Amar U. Kishan, MD, of the Department of Radiation Oncology, University of California, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Lantheus, Inc., and grants from the National Institutes of Health and Department of Defense. For full disclosures of all study authors, visit ascopubs.org.
