ONCOmmunity

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA.

By: Benedikt Feuerecker, Robert Tauber, Karina Knorr, Matthias Heck, Ali Beheshti, Christof Seidl, Frank Bruchertseifer, Anja Pickhard, Andrei Gafita, Clemens Kratochwil, Margitta Retz, Jürgen E Gschwend, Wolfgang A Weber, Calogero D'Alessandria, Alfred Morgenstern, Matthias Eiber

Department of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK), partnersite Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: benedikt.feuerecker@tum.de.
2020-04-01; doi: 10.1016/j.eururo.2020.11.013

Abstract

Background

Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.

Objective

To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.

Design,

Twenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.

Outcome

Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.

Results

Sixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8-11.2), 4.1 (95% CI 3-14.8), and 7.7 (95% CI 4.5-12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. 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

Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.