Louise Kostos, MBBS, FRACP, on combined radium-223 and LuPSMA in mCRPC

Data from the phase 1/2 AlphaBet trial (NCT05383079) were presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany. Overall, data showed that the combination of radium-223 and lutetium-177 PSMA-I&T was safe, well-tolerated, and had preliminary anti-tumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC).1

In a recent interview with Urology Times®, Louise K. Kostos, MBBS, FRACP, PhD candidate, outlined the key takeaways from the initial readout. Kostos is a medical oncologist at Peter MacCullum Cancer Centre in Melbourne, Australia.

In total, the study included 36 patients with progressive mCRPC following at least 1 androgen receptor pathway inhibitor. Patients also needed to have at least 2 untreated bone metastases on bone scane, PSMA-PET positive disease, and an ECOG performance status of 0 to 2.

The dose escalation phase included 9 patients to assess 2 dose levels of 223Ra (27.5 kBq/kg every 6 weeks or 55 kBq/kg every 6 weeks) combined with a fixed dose of LuPSMA (7.4 GBq every 6 weeks). The dose expansion phase included 27 additional patients to further evaluate the 223Ra dose of 55 kBq/kg every 6 weeks plus 7.4 GBq LuPSMA every 6 weeks.

The combination was found to be well-tolerated, with no dose-limiting toxicities reported. Grade 3 or higher treatment-related adverse events were observed in 14% of patients, which included anemia (n = 4), neutropenia (n = 3), and non-clinically significant lymphopenia (n = 10). There were no fractures or deaths.

Kostos added, “Prior studies with radium have found that there is an increased risk of fractures, but that is mitigated with bone protective therapy, which we did mandate in the AlphaBet study.”

Efficacy findings at a median follow-up of 13.3 months showed a radiographic progression-free survival (PFS) of 10 months (95% CI, 6.7 to 13.5). The median prostate-specific antigen (PSA) PFS was 5.3 months (95% CI, 4.0 to 9.0). Overall, 55% of patients achieved a PSA decline of at least 50%, and 18% of patients achieved a PSA decline of at least 90%.

Based on these data, the authors concluded, “The findings support further evaluation of combined alpha/beta-emitting approaches.”

REFERENCE

1. Kostos L, Buteau JP, Xie J, et al. A phase I/II trial of combined Radium-223 and Lutetium-177 PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC): First analysis of the AlphaBet trial. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 2386P