Tolerability of [177Lu]Lu-PSMA-617 by treatment exposure in patients with metastatic castration-resistant prostate cancer (mCRPC): A VISION study subgroup analysis.

Abstract

5047 Background: In the phase 3 VISION study, lutetium (177Lu) vipivotide tetraxetan ([177Lu]Lu-PSMA-617; 177Lu-PSMA-617) + protocol-permitted standard of care (SoC) improved clinical benefit and was generally well tolerated despite a higher rate of adverse events (AEs) than SoC alone. Here we assess AE incidence by exposure to 177Lu-PSMA-617. Methods: VISION was an international, open-label study of 177Lu-PSMA-617 in adults with PSMA-positive mCRPC previously treated with ≥ 1 androgen receptor pathway inhibitor and 1–2 taxane regimens. Patients received 177Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤ 6 cycles) + SoC or SoC alone. rPFS and OS were primary endpoints; safety was a secondary endpoint. AE analysis by exposure to 177Lu-PSMA-617 was carried out in pre-specified subgroups. 177Lu-PSMA-617 cycle duration was generally ̃6 weeks and cycle 6 duration was until the earliest date of subsequent treatment, and date of last administration of randomized treatment (including SoC) + 30 days. The cycle of onset in which an AE first occurred in a patient at maximum grade was assessed. Results: The median duration of cycle of onset for cycles 1 to 5 was 6 weeks; for cycle 6, it was 26.6 weeks (Table). Of the 529 patients in the 177Lu-PSMA-617 group, 240 (45.4%) received ≤ 4 cycles and 289 (54.6%) received 5–6 cycles of treatment. In patients who received ≤ 4 or 5–6 cycles, 234 (97.5%) and 285 (98.6%) treatment-emergent AEs (TEAEs); 100 (41.7%) and 92 (31.8%) serious TEAEs; 205 (85.4%) and 246 (85.1%) treatment-related AEs; and 13 (5.4%) and 6 (2.1%) fatal TEAEs, respectively, were observed. Number of TEAEs and serious TEAEs by cycle of onset are shown in the Table. Conclusions: Over 50% of patients with mCRPC received 5–6 cycles of 177Lu-PSMA-617. For cycles 1–5, TEAEs occurred at every cycle, with similar frequency. More TEAEs were observed in cycle 6, reflecting its longer median duration than other cycles. Clinical trial information: NCT03511664. [Table: see text]