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

Introduction: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 pre-treated metastatic castration-resistant prostate carcinoma patients. Here we report on treatment outcome and survival using this novel treatment modality in a series of 53 metastatic castration resistant prostate carcinoma patients directly following their androgen deprivation treatment. Patients and Methods:225Ac-PSMA-617 was administered to 53 mCRPC patients directly following their androgen deprivation therapy. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle and on follow-up for selection of patients for treatment, to determine the activity to be administered and for response assessment. Serial prostate specific antigen (PSA) was obtained for PSA response assessment. Results: The median age of the patient population under study was 63.4 yrs (range 45-83 years). A total number of 167 cycles were administered. The median number of cycles administered was 3 (range 1-7). Forty-eight patients (91%) had a PSA decline > 50%, and 51 patients (96%) had any decline in PSA . 68Ga-PSMA-PET images became negative in 30 patients. In the multivariate analysis a PSA decline > 50 % proved predictive of both PFS and OS whereas platelet count also proved predictive for PFS. Median estimated OS for patients with a PSA decline < 50% was 9 months whereas the median OS of those patients with a PSA decline > 50% was not yet reached at the date of latest follow-up (55 months). Estimated median PFS for patients with a PSA decline > 50% was 22 months whereas that for patients with a PSA decline < 50% was 4 months. No severe of hematotoxicity was noted, whiles only 3 patients had grade III-IV nephrotoxicity. The commonest toxicity seen was grade I-II xerostomia observed in 81% of patients. Conclusion: In this series on 53 patients suffering from mCRPC, treatment with 225Ac-PSMA-617 administered immediately following ADT, resulted in a > 50% decrease in PSA level in 91% of the patients. Furthermore, a PSA decline of greater than or equal to 50% proved the single most important factor predicting PFS and OS following 225Ac-PSMA-617 treatment. Of interest, median OS of those patients with a PSA decline > 50% was not yet reached at the date of latest follow-up (55 months). These very favorable results obtained suggest a prospective randomized study comparing 225Ac-PSMA-617 to current standard of care treatment options, e.g. enzalutamide, abiraterone acetate and docetaxel, post ADT is of major clinical relevance.