Background: Beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new treatment option for metastatic castration-resistant prostate cancer (mCRPC) but its antitumor effect can decrease over time. Purpose: To report safety and activity of alpha emitter Ac-225-PSMA-617 radioligand therapy in mCRPC that have progressed after Lu-177-PSMA RLT. Design, Setting, Participants: 26 mCRPC patients were treated under a compassionate use protocol. Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA RLT and positive PSMA-ligand uptake. Median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given 8 weekly until progression or intolerable side effects. Outcome measurements and statistical analysis: Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS) and toxicity. Results and Limitations: 59 cycles of Ac-225-PSMA-617 (median number of cycles 2, range 1-6) were administered. PSA-decline of 50% was achieved in 17/26 (65%) patients. Median PSA-PFS, cPFS and OS were 3.5 months [95%CI 1.8–11.2], 5 months [95% CI 3–14.8] and 7.7 months [95%CI 4.5–12.1], respectively. Visceral metastases were associated with shorter PSA-PFS (median 1.9 vs. 5.5 months; p=0.002), cPFS (median 3.0 vs. 5.3 months; p=0.03) and OS (median 5.4 vs. 12 months; p=0.046). Hematologic grade 3/4 toxicities were anemia (35%), leucopenia (27%) and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia and 6/26 (23%) patients subsequently terminated treatment. A limitation is the retrospective design. Conclusions: Ac-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late stage mCRPC. Grade 3-4 hematological side effects were observed in up to one third of patients and xerostomia led to treatment halt in a relevant number of patients. Patient summary: Ac-225-PSMA-617 therapy showed substantial antitumor effect in late mCRPC after Lu-177-PSMA failure. However, dry mouth is a common side effect which caused about a quarter of the patient to stop therapy.

FEUERECKER Benedikt;  TAUBER R;  KNORR Karina;  HECK M;  BEHESHTI A;  SEIDL C.;  BRUCHERTSEIFER Frank;  PICKHADT A;  GAFITA A;  KRATOCHWIL Clemens;  RETZ M;  GSCHWEND J.E.;  WEBER Wolfgang;  D'ALESSANDRIA C;  MORGENSTERN Alfred;  EIBER Matthias; 

2021-03-03

ELSEVIER SCIENCE BV

JRC120350

0302-2838 (online),   

https://www.sciencedirect.com/science/article/pii/S0302283820308770?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC120350,   

10.1016/j.eururo.2020.11.013 (online),