VISION Trial Follow-Up: Exposure Adjusted Rates of Treatment-Emergent Adverse Events

In a follow-up to the VISION trial, which evaluated 177Lu-PSMA-617 in patients with advanced prostate-specific membrane antigen (PSMA)-PET-positive metastatic castration-resistant prostate cancer, Kim N. Chi. MD, FRCPC, and colleagues compared associations of exposure and treatment-emergent adverse events (TEAEs) frequency between the study arms of VISION. Their study, presented in Poster Session A, Prostate Cancer, at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, found a comparable rate of TEAEs between arms, which they stated was confirmation of “a favorable risk/benefit profile of 177Lu-PSMA-617 added to [standard of care (SoC)] in this patient population.”

Patients in the VISION trial were adults, previously treated with one androgen receptor pathway inhibitor and one or two taxane regimens, who were randomized (2:1) to receive either 177Lu-PSMA-617 plus SoC, or SoC only. TEAEs were recorded from the start of treatment and up to 30 days after last treatment, or one day before subsequent anticancer therapy.

This follow-up report was designed primarily to address the fact that treatment exposure in the intervention arm was over three times longer than in the SoC arm. Investigators corrected for the discrepancy by calculating first TEAE incidence per 100 patient treatment-years (PTY).

In their analysis, the authors found a similar rate of gastrointestinal events and fatigue between SoC and the intervention arms. However, they calculated a higher adjusted incidence rate of musculoskeletal and renal events in the SoC arm compared to the intervention arm, which they suggested was evidence of an association with treatment exposure rather than with 177Lu-PSMA-617. Lastly, the authors confirmed the association between 177Lu-PSMA-617 treatment and higher incidence of dry mouth, dry eye, and acute myelosuppression.

The authors aimed to address the fact that the treatment regimen’s toxicity may have been overestimated due to the difference in treatment exposure between the arms. They concluded, per their exposure-adjusted analysis, that the rate of TEAEs was comparable, supporting the use of 177Lu-PSMA-617 for patients with PSMA-PET-positive metastatic castration-resistant prostate cancer.