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.
Clinical genitourinary cancer. 2026 Mar 27 [Epub ahead of print]
Jabra Zarka, Ronit Juthani, Oliver Sartor, Miguel Muniz, Adam M Kase, Irbaz B Riaz, Arsalan Naqvi, Elisabeth Heath, Jacob J Orme, Zachary Scharf, Gokce Belge Bilgin, Eugene D Kwon, Albert Jang, Ali Tarhini, Geoffrey B Johnson, Ayse Tuba Kendi, Matthew P Thorpe, Mrinal S Patnaik, Yael Kusne, Heather Jacene, Praful Ravi, Daniel S Childs
Department of Medical Oncology, Mayo Clinic, Rochester, MN; Division of Hematology, Mayo Clinic, Rochester, MN. Electronic address: ., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Department of Medical Oncology, East Jefferson General Hospital Cancer Center, New Orleans, LA., Department of Medical Oncology, Mayo Clinic, Rochester, MN., Department of Medical Oncology, Mayo Clinic, Jacksonville, FL., Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ., Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, MN., Department of Urology, Mayo Clinic, Rochester, MN., Division of Hematology, Mayo Clinic, Rochester, MN., Department of Imaging, Dana-Farber Cancer Institute, Boston, MA.