Abstract CT225: Quantitative assessment of PSMA imaging before and after 177Lu-PSMA-617 treatment in a Ph I/II trial

Abstract Background: We have previously reported that 177Lu-PSMA-617 given as a single-cycle, dose-intense regimen for patients (pts) with pretreated mCRPC is efficacious even without selection by PSMA (ESMO 2021). Quantitative analyses of pre-treatment PSMA PET may allow for better patient selection and prediction of toxicities. Analyses of sequential PET images may also provide insights that may be associated with longer term outcomes. Our previous analysis of 13 patients demonstrated association of PSMA PET signal with overall survival (OS) and PSA responses, as well as trends with adverse events (Nauseef GU ASCO 2022). Here we present long-term follow up data and expanded imaging correlatives from our completed phase I/II study. MethodsEntry criteria: progressive mCRPC after at least one prior potent AR pathway inhibitor and prior chemotherapy (excepting men ineligible for or refusing of chemotherapy) with allowance for prior radionuclides (incl. Ra223 and PSMA-TRTs). Treatment was fractionated-dose (D1 and D15) 177Lu-PSMA-617 (7. 4-22. 2 GBq). TRAQinform IQ (AIQ Solutions) was used to identify, track, and quantify regions of interest suspicious of cancer (lesion-ROI) on PSMA PET/CT images and quantify uptake in normal organs outside of lesion-ROI. Measurements included SUVmean across all lesion-ROI, volume of lesion-ROI, and SUVtotal (sum of SUV in all lesion-ROI), as well as changes after treatment, including in PSMA-expressing healthy tissues. Associations with survival were tested via Cox proportional hazard models in univariate analyses and associations with adverse events (AEs) and PSA responses were via assessed via Wilcoxon rank sum tests. Results32 pts (of 50 total in the study between 1/2017-2/2021) had pre- and post-treatment imaging suitable TRAQinform IQ analysis and associated survival analyses. Baseline characteristics were similar to the entire study cohort. PSA response of 50% was observed in 21/32 (66%) of which 16 were confirmed. No imaging variable predicted PSA30 or PSA50, although an association was observed in pretreatment SUVmean and lesion-ROI volume reduction. No imaging variable was significantly associated with OS (e. g. , pretx SUVmean HR 0. 9, p=0. 10, pretx Volume HR 1. 00, p=0. 052). Pretx SUVmean was associated with mPFS (HR 0. 85, 95% CI 0. 74, 0. 98, p=0. 023). Among select AEs, anemia was associated with non-lesion-ROI skeleton SUVtotal in pre- (p=0. 027) and post-tx (p=0. 007). Higher pre-treatment salivary gland uptake (SUVmean) was associated with more xerostomia (p=0. 11). Fatigue was associated with a variety of variables including salivary SUVs (mean, max, and total) and post-tx bowel SUVmax (p=0. 030). ConclusionsPre-treatment and pre- to post-treatment 68Ga-PSMA11-PET data analyzed may be associated with outcome. While a strength of this study is the prospective nature of patient enrollment and fixed imaging timepoints, our associations are limited by small sample size. Expansion of this analysis to larger datasets may improve our ability to predict treatment response and toxicity by body-wide PSMA detection. Citation Format: Jones Trevor Nauseef, Charlene Thomas, Michael Sun, Nicole Jacobs, Andrés Ricaurte Fajardo, Sam Ruder, Escarleth Fernandez, Zachary Davidson, Amie Patel, A. Oliver Sartor, Shankar Vallabhajosula, Ana Molina, Cora N. Sternberg, David M. Nanus, Sandra Huicochea Castellanos, Joseph Osborne, Neil H. Bander, Timothy Perk, Scott Tagawa. Quantitative assessment of PSMA imaging before and after 177Lu-PSMA-617 treatment in a Ph I/II trial abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT225.