[⁶⁸Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [¹⁷⁷Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy.

5002 Background: In the phase 3 VISION study, gallium ( 68 Ga) gozetotide ( 68 Ga-PSMA-11) PET/CT imaging was used to determine eligibility for lutetium ( 177 Lu) vipivotide tetraxetan ( 177 Lu-PSMA-617). Given that 177 Lu-PSMA-617 targets PSMA, we assessed the association between quantitative PSMA imaging parameters and treatment outcomes. Methods: In VISION, adults with mCRPC with ≥ 1 PSMA-positive (+) and no PSMA-negative lesions meeting the exclusion criteria were enrolled. In this sub-study, the association between imaging data from pre-enrollment 68 Ga-PSMA-11 PET/CT scans of pts in the 177 Lu-PSMA-617 group and clinical outcomes was assessed. Imaging data meeting quality requirements were analyzed for 548/551 pts. PSMA expression was quantified by 5 PET parameters: PSMA+ lesions by region, mean standardized uptake value (SUV mean ), maximum SUV (SUV max ), PSMA+ tumor volume, and tumor load (PSMA+ tumor volume × SUV mean ). Parameters were extracted from the whole body and 4 regions. Association between PET parameters and radiographic progression-free survival (rPFS; primary objective), overall survival (OS), objective response rate (ORR), and prostate–specific antigen 50 (PSA50) response was assessed. Results: Most pts (92.7%) had PSMA uptake in bone. In both the whole-body and regional analyses, statistically significant associations of PSMA PET parameters to clinical outcomes were observed (whole-body data shown in Table). Higher whole-body SUV mean was associated with improved clinical outcomes; pts in the highest quartile (SUV mean : rPFS, ≥ 10.2; OS, ≥ 9.9) had a median rPFS and OS of 14.1 and 21.4 months, vs 5.8 and 14.5 months for those in the lowest quartile (< 6.0; < 5.7), respectively. Absence of PSMA+ lesions in bone, liver, and lymph node, and lower PSMA+ tumor load, were indicators of good prognosis. Conclusions: Higher SUV mean is strongly associated with improved outcomes with 177 Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of 68 Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.[Table: see text]