[<sup>68</sup>Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [<sup>177</sup>Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy.
Phillip H. Kuo, Jacob Hesterman, Kambiz Rahbar, A. Tuba Kendi, Xiao X. Wei, Bruno Fang, Nabil Adra, Andrew J. Armstrong, Rohan Garje, Jeff M. Michalski, Samson Ghebremariam, Marcia Brackman, Connie Wong, Taylor L. Benson, Nicholas J. Vogelzang
Abstract
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]