Dosimetry of 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer: results from the VISION trial sub-study.
Authors: Herrmann Ken , Rahbar Kambiz , Eiber Matthias , Krause Bernd J. , Lassmann Michael , Jentzen Walter , Blumenstein Lars , Klein Patrick , Basque Jean-René , Kurth Jens 
Published: February 2022

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Background: The phase 3 VISION trial (NCT03511664) evaluated the efficacy and safety of the radioligand [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with metastatic castration-resistant prostate cancer. 177Lu-PSMA-617 plus protocol-permitted standard of care (SOC) significantly improved overall survival and radiographic progression-free survival of patients compared with SOC alone. The incidence of adverse events (AEs) of grade 3 or above was higher with 177Lu-PSMA-617 than without, but quality of life was not adversely affected. This dosimetry sub-study aimed to quantify the absorbed dose of 177Lu-PSMA-617 in organs at risk of radiotoxicity due to exposure levels or radiosensitivity. Methods: In a sub-study of VISION, dosimetry was performed in a separate cohort of 29 non-randomized participants at four German sites. Eligible patients received 177Lu-PSMA-617 (7.4 GBq per cycle) plus SOC every 6 weeks for a maximum of 6 cycles. Patients underwent planar whole-body scintigraphy scans and single-photon emission computed tomography/computed tomography (SPECT/CT) scans of the upper and lower abdomen at 2, 24, 48 and 168 hours after first administration. Blood and urine samples were collected throughout cycle 1. 177Lu-PSMA-617 dosimetry outcomes were based on biodistribution, assessed using whole-body conjugate planar-image data, SPECT/CT image data, blood assay data and urinary excretion data. Radiation exposure was estimated using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) software code version 2.2. Results were expressed as absorbed dose per unit activity (Gy/GBq) and cumulative estimated absorbed dose (Gy) over all 6 cycles (44.4 GBq cumulative activity) extrapolated from cycle 1 data. Results: Radiation-absorbed doses per unit activity were highest in the lacrimal glands, followed by the salivary glands, with mean values of 2.1 Gy/GBq (standard deviation [SD], 0.47) and 0.63 Gy/GBq (0.36), respectively. The kidneys received 0.43 Gy/GBq (SD, 0.16) and the blood-based red marrow dose was 0.035 Gy/GBq (0.02). The 6-cycle cumulative estimated absorbed dose was 92 Gy (SD, 21) in the lacrimal glands, 28 Gy (16) in the salivary glands, 19 Gy (7.3) in the kidneys and 1.5 Gy (0.90) in the red marrow. In cycle 1, 20% of patients had at least one hematological AE of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2; no patient experienced any renal AE of CTCAE grade ≥ 2 or any lacrimal gland toxicity, and 2 patients had a grade 1 salivary gland AE. Conclusions: 177Lu-PSMA-617 dosimetry results in this sub-study were consistent with the published ranges, and cycle 1 AEs affecting at-risk organs were infrequent and of low-to-moderate severity. These findings indicate that patients with metastatic castration-resistant prostate cancer receiving 177Lu-PSMA-617 should be at low risk of radiation-induced AEs. Clinical trial information: NCT03511664.