872PSafety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA

Abstract Background The treatment of mCRPC is a major medical challenge. The beta-emitting Lu-177-PSMA radioligand therapy (RLT) is a new option but its antitumor effect can decrease over time. The aim of this retrospective analysis was to investigate safety and efficacy of the alpha emitting Ac-225-PSMA-617 RLT in mCRPC after Lu-177-PSMA failure. Methods At data analysis 03/19 18 patients (pts) underwent Ac-225-PSMA-617 RLT between 10/17 and 12/18. All pts had previously received second line antihormonal treatment and 17/18 pts taxane based chemotherapy. All pts had shown progression after Lu-177-PSMA therapy (median 2 cycles). High PSMA-expression of the tumor lesions in PSMA-PET/CT before Ac-225-PSMA-617 was mandatory. Pts were treated at 8 weekly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) and blood cell count were measured every 2-3 weeks. We report updated data of hematological and non-hematological side effects, biochemical response and a subgroupanalysis. Results A total of 36 cycles of Ac-225-PSMA-617 (median dose 8 MBq, range 4,4–12.8) were applied. 7 pts received only 1 cycle, 5 pts 2 cycles, 5 pts 3 cycles and 1 patient 4 cycles. Baseline PSA was 822 ng/ml (range 49–4073). ECOG score was grade 0, 1 and 2 in 3, 13 and 2 pts. 15/18 pts showed any PSA-decline, 5/18 a PSA-decline of more than 50% and 3 pts no PSA-decline at any time. 6 weeks after treatment 12/18 showed any PSA decline and 4/18 a PSA-decline of > 50%. Grade 1 xerostomia occurred in 17 and grade 2 in 1 patient. 6/18 pts (33%) requested to stop treatment due to xerostomia. 2 pts developed grade 2 renal insufficiency, 5 pts grade 3-4 anemia, 2 pts grade 3-4 thrombocytopenia and 2 pts 3-4 leucopenia. 7/18 pts died during the observation period (median overall survival 9,6 months). The PSA-progression free survival was 1,3 months. In a subgroupanalysis of 9 pts with a rapid progression under a previous Lu-177-PSMA treatment 7 pts achieved any PSA-decline and 4 pts a decline of more than 50%. Conclusions In this small cohort Ac-225-PSMA-617 RLT showed antitumor effect in mCRPC after Lu-177-PSMA failure even after rapid tumour progression. However, treatment had to be stopped in one third of the pts due to xerostomia. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.