Activity and adverse events of actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of lutetium-177-PSMA
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-emittin...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2021
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| In: |
European urology
Year: 2021, Volume: 79, Issue: 3, Pages: 343-350 |
| ISSN: | 1873-7560 |
| DOI: | 10.1016/j.eururo.2020.11.013 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.eururo.2020.11.013 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0302283820308770 
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| Author Notes: | 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 |
MARC
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| 245 | 1 | 0 | |a Activity and adverse events of actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of lutetium-177-PSMA |c 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 |
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| 520 | |a 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, setting, and participants - 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 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 were measured. - Results and limitations - 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 summary - 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. | ||
| 650 | 4 | |a Ac-225-PSMA-617 | |
| 650 | 4 | |a Metastatic castration-resistant prostate cancer | |
| 650 | 4 | |a Overall survival | |
| 650 | 4 | |a Prostate-specific antigen decline | |
| 650 | 4 | |a Radioligand therapy | |
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