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

Clin Genitourin Cancer. 2019 Feb;17(1):15-22. doi: 10.1016/j.clgc.2018.09.014. Epub 2018 Sep 27.

Abstract

Background: 177Lu-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 68Ga-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 18F-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.

Keywords: FDG; Lutetium PSMA therapy; Positron emission tomography; Prostate cancer; Prostate specific membrane antigen.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dipeptides / therapeutic use*
  • Disease Progression
  • Follow-Up Studies
  • Heterocyclic Compounds, 1-Ring / therapeutic use*
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Lutetium / therapeutic use*
  • Male
  • Middle Aged
  • Pilot Projects
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Prospective Studies
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Prostatic Neoplasms, Castration-Resistant / secondary
  • Radioisotopes / therapeutic use*
  • Survival Rate

Substances

  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • PSMA-617
  • Radioisotopes
  • Lutetium
  • Lutetium-177
  • Prostate-Specific Antigen