LuRa: Efficacy and Safety of Radium-223 Following [¹⁷⁷Lu]Lu-PSMA-617 in Patients With Metastatic Castration-Resistant...

Approval of [177Lu]Lu-PSMA-617 has changed the usual sequencing of treatments for metastatic castration-resistant prostate cancer (mCRPC). There is limited data on outcomes and safety of therapies used after its administration.

We conducted a retrospective, multi-institutional analysis including patients with mCRPC who received Radium-223 (Ra-223) after [177Lu]Lu-PSMA-617. Patients from Mayo Clinic and Dana-Farber Cancer Institute were evaluated for multiple efficacy and tolerability endpoints, with particular attention given to hematologic toxicities and skeletal-related events.

Among 21 patients analyzed, 19% (n = 4) completed all 6 planned Ra-223 cycles. Reasons for early treatment discontinuation included: disease progression (n = 13, 62%) and toxicity (n = 2, 10%). Hematologic toxicity included grade ≥ 3 anemia and thrombocytopenia in 33% (n = 7) and 19% (n = 4) of patients, respectively, and 38% (n = 8) required transfusions, all of which occurred within 30 days following the final Ra-223 cycle. Four patients (19%) developed new skeletal-related events after starting Ra-223. One PSA50 response was observed and ≥ % reduction in alkaline phosphatase levels occurred in 42% of patients (n=9). The median PSA progression-free survival was 2.5 months (95% CI; 1.4 - 3.8 months). The median overall survival was 10.6 months (95% CI; 5.2 - 20.4 months) and 76% (n = 16) of patients survived six months beyond their first dose of Ra-223.

These data suggest that Ra-223 after [177Lu]Lu-PSMA-617 is feasible with efficacy even amongst heavily pre-treated patients. The observed hematologic toxicities and fractures underscore the need for careful patient selection and monitoring.