Examining laboratory-based VISION eligibility and <sup>177</sup>Lu-PSMA-617 outcomes in patients with metastatic castration-resistant prostate cancer.
Authors: Alireza Ghodsi, Ridvan Arda Demirci, Roman Gulati, Ruben Raychaudhuri, Heather H. Cheng, Jessica E. Hawley, Todd Yezefski, Michael C. Haffner, Robert Bruce Montgomery, Peter Nelson, Michael Thomas Schweizer, Evan Y. Yu, Delphine L. Chen, Amir Iravani
Journal: Journal of Clinical Oncology (2024)

e17062 Background: Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA-617) is an FDA-approved therapy for metastatic castration-resistant prostate cancer (mCRPC) and commonly used in late-line treatment for patients with extensive disease and diminished organ function. It is unclear whether patients with low bone marrow reserve derive benefit from the treatment. The study aimed to evaluate outcomes of treating mCRPC patients with 177 Lu-PSMA-617, classifying them as either VISION-Eligible (VISION-E) or VISION-Ineligible (VISION-I) based on baseline laboratory test results. Methods: This retrospective cohort study evaluated patients who had received at least one cycle of 177 Lu-PSMA-617 between June 2022 and July 2023. Eligible patients were then classified as VISION-E or VISION-I using VISION trial eligibility criteria: white blood cell (WBC) count ≥2.5 × 10 9 /L or absolute neutrophil count ≥1.5 × 10 9 /L, platelets (PLT) ≥100 × 10 9 /L, hemoglobin (Hb) ≥9 g/dL, total bilirubin ≤1.5 × upper limit of normal (ULN), ALT or AST ≤3.0 × ULN, serum creatinine ≤1.5 × ULN, and albumin &gt;3.0 g/dL. PSA decline of at least 50% relative to baseline (PSA50), PSA-progression-free survival (PSA-PFS), and overall survival (OS), were evaluated using tests of proportions or Cox regressions. Results: In our study of 123 patients (median age: 73 years, median cycles: 4), 85.4% had ECOG 0 or 1. 75.6% of the cohort were VISION-E, while 24.4% were VISION-I. No substantial differences were observed in baseline characteristics between the two groups, including age (p-value: 0.7) and ECOG (p-value: 0.5). Among VISION-I patients, 73.3% did not meet the threshold for hematologic lab results (16 patients with low Hb, 5 with low PLT, and 4 with low WBC), while 13.3% did not meet criteria for renal lab tests and an additional 13.3% did not meet criteria for liver lab tests. Overall, 52% of patients showed a PSA50, and the median PSA-PFS and OS of the total patient cohort were 9 (95% CI: 7.8-10.2) months and 11 (95% CI: 9.9-12.1) months, respectively. No statistically significant differences in PSA50 were observed between VISION-E (55.9%, 95% CI: 45%-66%) and VISION-I patients (40%, 95% CI: 23%-59%) (p: 0.13). The PSA-PFS and OS were not statistically significant different between VISION-E and VISION-I groups (median OS not reached vs. 13 months, p: 0.4, and median PSA-PFS of 4 months vs. 5 months, p: 0.5) (Table). Conclusions: In this study, the patients who did not meet VISION laboratory thresholds did not have statistically significant different PSA50, PSA-PFS and OS compared to those who met the criteria. A more lenient laboratory threshold appears to be acceptable for treatment with 177 Lu-PSMA-617. [Table: see text]