Results of a Prospective Phase 2 Pilot Trial of 177Lu-PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer Including Imaging Predictors of Treatment Response and Patterns of Progression

This study examined the value of Ga-68-HBEDD (PSMA-11; prostate-specific membrane antigen, PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-177 PSMA-617 (Lu-PS MA) therapy within the context of a phase 2 prospective pilot trial. The study found that a minimum intensity of tumor activity is required on PSMA PET to get a treatment response to Lu-PSMA therapy. Background: Lu-177-PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of Ga-68-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial. Patients and Methods: Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no F-18-Fluoro-deoxyglucose (FDG) PET-discordant disease. Men received up to 4 cycles of Lu-PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate-specific antigen (PSA) progression. The study assessed treatment response to Lu-PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment. Results: Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A >= 50% reduction in PSA occurred in 5 (36%), and >= 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of >= 30% PSA reduction: SUV max value 17 +/- 9 versus 44 +/- 15 (P < .007), and PSMA SUV mean 6 +/- 4 versus 10 +/- 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted >= 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression. Conclusion: PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options. (C) 2018 Elsevier Inc. All rights reserved.