Background: Treatment of advanced metastatic castration resistant prostate cancer (mCRPC) after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA) targeting β- and α-emitters have been introduced with promising response rates. Here, we present the first clinical data for PSMA targeted α-therapy (TAT) using 225Ac-PSMA-I&T. Methods: 18 patients receiving 225Ac-PSMA-I&T have been included in this retrospective analysis. 15/18 had prior second line antiandrogen treatment with abiraterone and/or enzalutamide, 15/18 prior chemotherapy and 13/18 prior 177Lu-PSMA treatment. Patients were treated at bi-monthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematological and non-hematological side effects were recorded according to CTCAE v5.0 criteria. Results: 38 cycles of 225Ac-PSMA-I&T were applied (median dose 7.8 MBq, range 6.0 - 8.5) with 1 cycle in 7/18, 2 cycles in 7/18, 4 cycles in 3/18 and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 176 ng/ml (range 13.4 - 1146). 4/18 patients were excluded due to incomplete follow-up. Best PSA response after TAT with a PSA decline ≥ 50% was oberved in 7/14 patients. Any PSA decline was seen in 11/14 patients. 3 patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177Lu-177-PSMA treatment showed any PSA decline in 8/11 and a PSA decline ≥ 50% in 5/11 patients. Therapy related adverse events included deteroriation from grade 1 anemia baseline to grade 2 and grade 3 anemia in 4/14 and 1/14 patients after TAT, respectively. Grade 3 leukopenia was observed in 1 patient. Newly diagnosed grade 1 and grade 2 xerostomia was observed in 2 and 3 patients, respectively. However, including pre-existing xerostomia after prior 177Lu-177 PSMA, 8/14 patients had grade 1 and 5/14 grade 2 xerostomia after TAT. No further grade 3/4 hematological or non-hematological toxicities were observed. Conclusion: Our first clinical data for TAT using 225Ac-PSMA-I&T showed promising antitumor effect in advanced mCRPC even after failure of prior 177Lu-PSMA treatment with tolerable side effects. These results are highly comparable to data on 225Ac-PSMA-617 TAT.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020 Oct 02 [Epub ahead of print]
Mathias Johannes Zacherl, Franz Josef Gildehaus, Lena Mittlmeier, Guido Boening, Astrid Gosewisch, Vera Wenter, Nina-Sophie Schmidt-Hegemann, Claus Belka, Alexander Kretschmer, Jozefina Casuscelli, Christian G Stief, Marcus Unterrainer, Peter Bartenstein, Andrei Todica, Harun Ilhan
Department of Nuclear Medicine, University Hospital, LMU Munich, Germany., Department of Radiation Oncology, University Hospital, LMU Munich, Germany., Department of Urology, University Hospital, LMU Munich, Germany.