Abstract
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Objectives: The objective of this study is to evaluate the safety and therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy (TAT) in metastatic castration resistant prostate cancer patients (mCRPC).
Methods: The study has been approved by the Institute Ethics Committee (IEC:518). 28 mCRPC patients refractory to therapy options including first and second generation anti-androgen therapies, taxane-based chemotherapies, and 177Lu-PSMA-617 therapy were treated with 225Ac-PSMA-617 TAT (100 KBq/Kg body weight) at an interval of 8 weeks up to 7 cycles. The patients were treated from April 2018 to November 2019 with median follow-up duration was 9 months (range: 3 - 22 months). Hematologic, kidney, liver function tests and prostate specific antigen tests were repeated before and after every cycle of 225Ac-PSMA-617 TAT at 2, 4 and 8-week intervals. Treatment related side effects were assessed every 2 weeks on the basis of physical examination, vital signs, laboratory results (hematologic, kidney and liver function levels) and adverse events graded according the CTCAE v5.0. Response assessment included biochemical and molecular tumor response which were evaluated by the trend in PSA levels and follow-up 68Ga-PSMA PET/CT scan using PERCIST 1 criteria.
Results: The mean age of patients was 69.7 years (range: 46-87 years). 27/28 patients demonstrated extensive PSMA avid skeletal metastases on baseline 68Ga-PSMA PET/CT scan and in one patient disease was confined to primary and lymph node metastases. The median activity administered was 19.129 MBq (571µCi) ranging from 9.25 MBq to 62.9 MBq (250 to 1700 µCi) with a median of 3 cycles and were followed-up over a median duration of 9 months. At 2-3 month interval after the first therapy and the end of the assessment, >50% decline in PSA was observed in 25% and 32.1%, respectively. No patient experienced grade 3 or 4 hematologic or kidney toxicity. Regarding the liver function parameters, a decrease in the alkaline phosphatase values was observed in all the patients post-treatment (baseline: 441.8 U/L, post-therapy: 338.5 U/L, P<0.2426). Grade 1 or 2 xerostomia was observed in 6/28 patients. Molecular tumor response by PERCIST 1 criteria was conducted in 22/28 patients which revealed complete response in 1/22 (4.5%), partial response in 11/22 (50%) patients, 3/22 (13.6%) with stable disease, and 7/22 (31.7%) with progressive diseases. The disease control rate according to molecular response was 68%. The median overall survival was 17 months and median progression-free survival was not reached. 4 patients died during the treatment period.
Conclusions: None of the patients demonstrated grade 3 or 4 hematologic or kidney function toxicity and xerostomia. 225Ac-PSMA-671 TAT showed promising anti-tumor activity, sustained response and low treatment-related toxicities.