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J Nucl Med. 2018 May;59(5):795-802. doi: 10.2967/jnumed.117.203539. Epub 2018 Jan 11.

Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control.

Author information

1
Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany clemens.kratochwil@med.uni-heidelberg.de.
2
Directorate for Nuclear Safety and Security, Joint Research Centre, European Commission, Karlsruhe, Germany.
3
Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
4
Department of Urology, University Hospital Heidelberg, Heidelberg, Germany; and.
5
Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

The aim of this evaluation was to identify the first indicators of efficacy for 225Ac-labeled prostate-specific membrane antigen (PSMA)-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with three 100 kBq/kg cycles of 225Ac-PSMA-617 at 2-mo intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 wk. PSMA PET/CT or PSMA SPECT/CT were used for baseline staging and imaging follow-up at month 6. Follow-up included the duration of PSA response and radiologic progression-free survival at month 6. Patient histories were reviewed for the duration of previous treatment lines, and a swimmer plot was used to intraindividually compare the duration of tumor control by PSMA therapy versus prior treatment modalities. Results: Thirty-one of 40 patients were treated per protocol. Five patients discontinued treatment because of nonresponse, and 4 because of xerostomia. Of the 38 patients surviving at least 8 wk, 24 (63%) had a PSA decline of more than 50%, and 33 (87%) had a PSA response of any degree. The median duration of tumor control under 225Ac-PSMA-617 last-line therapy was 9.0 mo; 5 patients had an enduring response of more than 2 y. Because all patients had advanced disease, this result compares favorably with the tumor control rates associated with earlier-phase disease; the most common preceding first-, second-, third-, and fourth-line therapies were abiraterone (median duration 10.0 mo), docetaxel (6.5 mo), enzalutamide (6.5 mo), and cabazitaxel (6.0 mo), respectively. Conclusion: A positive response for surrogate parameters demonstrates remarkable antitumor activity for 225Ac-PSMA-617. Swimmer-plot analysis indicates a promising duration of tumor control, especially considering the unfavorable prognostic profile of the selected advanced-stage patients. Xerostomia was the main reason patients discontinued therapy or refused additional administrations and was in the same dimension as nonresponse; this finding indicates that further modifications of the treatment regimen with regard to side effects might be necessary to further enhance the therapeutic range.

KEYWORDS:

225Ac; Ac-225; PSMA; prostate cancer; targeting therapy

PMID:
29326358
DOI:
10.2967/jnumed.117.203539

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