The DUET-1 trial: Feasibility and toxicity outcomes and early oncological outcomes of ¹⁷⁷ lutetium-PSMA radioligand therapy (RLT) alternated with ²³³ radium-dichloride in patients with metachronous oligorecurrent osseus hormone sensitive prostate cancer (mHSPC).

Abstract

e17083 Background: Currently, no available therapy has been shown to significantly improve long-term oncological outcomes in patients with metachronous bone-oligometastatic hormone-sensitive prostate cancer (HSPCa). Combining alpha- and beta-particle treatments—specifically ²²³[Ra]Radium-dichloride and ¹⁷⁷[Lu]Lutetium-PSMA—may confer greater therapeutic benefit when initiated during earlier phases of disease such as in patients with metachronous bone-oligometastatic HSPCa. Methods: The DUET-1 trial was a prospective, single-arm, phase I–II study conducted at Amsterdam University Medical Center in the Netherlands. The study enrolled six patients with metachronous oligorecurrent bone-metastatic HSPCa following curative therapy such as radical prostatectomy or external beam radiotherapy. All participants had oligometastatic prostate cancer on PSMA PET/CT, defined as one to five bone metastases, and an ECOG performance status of 0–1. Patients received 3 cycles of ²²³Ra-dichloride (55kBq/kg) at 0,4 and 8 weeks and 2 cycles of ¹⁷⁷Lu-PSMA (7.4 GBq/cycle) at 6 and 12 weeks. The primary endpoint was feasibility of 223 Ra-dichloride and 177 Lu-PSMA radioligand therapy (RLT), toxicity, adverse events (AE) and patient reported outcomes (HRQoL and xerostomia inventory). Secondary endpoints were biochemical response (prostate-specific antigen (PSA) and alkaline phosphatase (AFP) levels) at 3 mo. post-treatment and radiological progression free survival (rPFS) at 3 mo. post-treatment. Results: Six patients were enrolled between January 2025 and October 2025 of whom 5 had reached three months of follow-up. All patients were able to complete radioligand therapy (RLT) without any interruptions or delays. No serious adverse events were reported during the treatment period. There were no hematological toxicities observed in any of the patients. Only mild adverse events occurred, specifically grade 1 xerostomia and grade 1 fatigue. Patients maintained health-related quality-of-life scores that were comparable to their baseline assessments. At three months after initiation of therapy, no PSA progression was observed in 3/5 patients and no AFP progression was observed in 5/5 patients. Stable radiological disease or a mixed response was seen in 3/5 patients. Conclusions: Dual RLT with 3 cycles of ²²³[Ra]Radium-dichloride and 2 cycles of ¹⁷⁷[Lu]Lutetium-PSMA in patients with metachronous oligorecurrent osseous mHSPC is safe, is feasible, and has hardly any impact on HRQoL. It has a promising biochemical response and provides for a mixed radiological response with stable disease in some patients on follow-up.