Deescalated 225Ac-PSMA-617 Versus 177Lu/225Ac-PSMA-617 Cocktail Therapy: A Single-Center Retrospective Analysis of 233 Patients.

Rathke, Hendrik; Winter, Erik; Bruchertseifer, Frank; Röhrich, Manuel; Giesel, Frederik Lars; Haberkorn, Uwe; Morgenstern, Alfred; Kratochwil, Clemens (2024). Deescalated 225Ac-PSMA-617 Versus 177Lu/225Ac-PSMA-617 Cocktail Therapy: A Single-Center Retrospective Analysis of 233 Patients. Journal of nuclear medicine, 65(7), pp. 1057-1063. Society of Nuclear Medicine and Molecular Imaging 10.2967/jnumed.123.267206

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The aim of this work is to evaluate our clinical real-world data obtained with 225Ac-PSMA-617 (AcPSMA), which were acquired under compassionate care regulations in patients with advanced-stage prostate cancer. The objective parameters that could be derived from this evaluation are compared with previous literature about AcPSMA and 177Lu-PSMA-617 (LuPSMA). Methods: The medical files of all patients who had received AcPSMA on an individual patient basis at the Heidelberg University Hospital since January 2014 were analyzed retrospectively. Previously published patients were excluded. The remaining patients were tailored into 2 subgroups with different treatment strategies: group 1 received AcPSMA as a deescalated monotherapy, and group 2 received LuPSMA plus AcPSMA as a cocktail regimen. Baseline characteristics, serum prostate-specific antigen (PSA) response, and overall survival were compared with the most appropriate historical controls. Results: Of 287 patients treated, 54 were excluded because of previous publication and 233 were evaluated, 104 of whom received AcPSMA monotherapy (median, 6 MBq). In this group, 55 patients (53%) presented with a best PSA response of at least 50%. The other 129 patients received a cocktail therapy of AcPSMA (median, 4 MBq) plus LuPSMA (4 GBq). In this group, a best PSA response of at least 50% was observed in 74 patients (57%). The median overall survival in the monogroup was 9 mo and in the cocktail group was 15 mo. If adjusted for prognostic baseline characteristics, the efficacy of both regimens was not significantly different. Conclusion: Deescalated treatment activities of AcPSMA or AcPSMA and LuPSMA cocktail regimens present better tolerability with regard to xerostomia than previous regimens of at least 100 kBq/kg while retaining high antitumor activity in poor-prognosis prostate cancer patients.

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