mCRPC Patients Receiving 225 Ac-PSMA-617 Therapy in the Post–Androgen Deprivation Therapy Setting: Response to Treatment and Survival Analysis

The Journal of Nuclear Medicine

article

Mike Sathekge¹  Frank Bruchertseifer²  Mariza Vorster¹  Ismaheel O. Lawal¹  Otto Knoesen³  Johncy Mahapane¹  Cindy Davis¹  Amanda lophane⁴  Alex Maes¹  Kgomotso Mokoala¹  Kgomotso Mathabe⁵  Christophe Van¹  de Wiele¹  Alfred Morgenstern¹ 

[1] Department of Nuclear Medicine;European Commission, Joint Research Centre;Nuclear Technology Products;Nuclear Medicine Research Infrastructure;Department of Urology;University of Pretoria and Steve Biko Academic Hospital;Ghent University

关键词: 225Ac-PSMA;    ADT;    therapy response;    PSA response;    prostate carcinoma;   

DOI  :  10.2967/jnumed.121.263618

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

225Ac-PSMA-617, targeting the prostate-specific membrane antigen (PSMA), which is overexpressed on prostate cancer cells, has shown a remarkable therapeutic efficacy in heavily pretreated patients with metastatic castration-resistant prostate carcinoma (mCRPC). Here, we report on treatment outcome and survival using this novel treatment modality in a series of 53 patients with mCRPC directly after their androgen deprivation treatment (ADT). Methods: 225Ac-PSMA-617 was administered to 53 such patients. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up to select patients for treatment, determine the activity to be administered, and assess their response. Serial prostate-specific antigen (PSA) measurements were obtained for response assessment. Results: The median age of the patients was 63.4 y (range, 45–83 y). In total, 167 cycles were administered (median, 3; range, 1–7). Forty-eight patients (91%) had a PSA decline of at least 50%, and 51 patients (96%) had any decline in PSA. 68Ga-PSMA PET findings became negative in 30 patients. In the multivariate analysis, a PSA decline of at least 50% proved predictive of both progression-free survival (PFS) and overall survival (OS), and platelet count also proved predictive for PFS. The median estimated OS was 9 mo for patients with a PSA decline of less than 50% but was not yet reached at the latest follow-up (55 mo) for patients with a PSA decline of 50% or more. The estimated median PFS was 22 mo for patients with a PSA decline of at least 50% and 4 mo for patients with a PSA decline of less than 50%. No severe hematotoxicity was noted, and only 3 patients had grade III–IV nephrotoxicity. The commonest toxicity seen was grade I–II xerostomia, observed in 81% of patients. Conclusion: In 91% of 53 patients with mCRPC, treatment with 225Ac-PSMA-617 immediately after ADT resulted in at least a 50% decrease in PSA level. Furthermore, a PSA decline of at least 50% proved the single most important factor predicting PFS and OS after 225Ac-PSMA-617 treatment. Of interest, median OS in patients with a PSA decline of at least 50% was not yet reached at the latest follow-up (55 mo). These favorable results suggest that it would be of major clinical relevance to perform a prospective randomized study comparing 225Ac-PSMA-617 with current standard-of-care treatment options such as enzalutamide, abiraterone acetate, and docetaxel after ADT.

【 授权许可】

CC BY