First Clinical Results for PSMA-Targeted alpha-Therapy Using Ac-225-PSMA-I&T in Advanced-mCRPC Patients

Zacherl, Mathias Johannes; Gildehaus, Franz Josef; Mittlmeier, Lena; Boening, Guido; Gosewisch, Astrid; Wenter, Vera; Unterrainer, Marcus; Schmidt-Hegemann, Nina; Belka, Claus; Kretschmer, Alexander; Casuscelli, Jozefina; Stief, Christian G.; Unterrainer, Marcus; Bartenstein, Peter; Todica, Andrei und Ilhan, Harun (2021): First Clinical Results for PSMA-Targeted alpha-Therapy Using Ac-225-PSMA-I&T in Advanced-mCRPC Patients. In: Journal of Nuclear Medicine, Bd. 62, Nr. 5: S. 669-674

Abstract

Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting beta- and alpha-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted a-therapy (TAT) using Ac-225-PSMA imaging and therapy (I&T). Methods: Fourteen patients receiving Ac-225-PSMA-I&T were included in this retrospective analysis. Eleven of the 14 had prior second-line antiandrogen treatment with abiraterone or enzalutamide, prior chemotherapy, and prior Lu-177-PSMA treatment. Patients were treated at bimonthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematologic and nonhematologic side effects were recorded according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Thirty-four cycles of 225 ACPSMA-I&T were applied (median dose, 7.8 MBq;range, 6.0-8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5-818 ng/mL). The best PSA response after TAT (a PSA decline >= 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior Lu-177-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after Lu-177-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion: Our first clinical data for TAT using Ac-225-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on Ac-225-PSMA-617 TAT.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0161-5505
• Sprache: Englisch