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2019 John Black Charitable Foundation-PCF Challenge Award

Expression-Based Treatment Stratification of Hormone-Sensitive Prostate Cancer Starting Long-Term Androgen Deprivation Therapy in the Multi-Centre STAMPEDE Platform Trial

Principal Investigators: Gerhardt Attard, MD, PhD (University College London), Mahesh Parmar, MSc (University College London), Noel Clarke, MBBS (The Christie NHS Foundation Trust)

Co-Investigators: Marina Parry, PhD (University College London), Daniel Berney, MBBS (Queen Mary University of London), Louise Brown, PhD (University College London), Nicholas James, MBBS, PhD (Queen Elizabeth Hospital)

Description:

  • Recent phase III clinical trials have established that in men with metastatic hormone sensitive prostate cancer (mHSPC) who are starting treatment with long-term androgen deprivation therapy (ADT), the addition of docetaxel chemotherapy or androgen receptor (AR)-targeted therapies (abiraterone, enzalutamide, apalutamide, darolutamide) can improve progression free and/or overall survival. However, it is still unclear whether certain men would benefit most from ADT alone, or a specific combination therapy.
  • Dr. Gerhardt Attard and team are studying whether certain men would benefit most from ADT alone vs. ADT + an AR-targeted therapy, using patient samples from the STAMPEDE clinical trial.
  • STAMPEDE is a multi-arm, multi-stage randomized clinical trial being conducted in Europe (UK and Switzerland) that is comparing the efficacy of several different treatment regimens in men with prostate cancer who are starting long-term ADT. One practice-changing finding made by STAMPEDE was that the addition of abiraterone in men starting ADT improves overall survival.
  • In this project, Dr. Attard and team will investigate gene expression in tumors from patients on STAMPEDE who were randomized to receive ADT vs. ADT + abiraterone. This data will be used to develop and validate a gene expression-based biomarker to identify patients that derive the greatest benefit from addition of AR-targeted therapy to ADT.
  • The team will investigate whether radiological disease volume, pattern of metastases at presentation, and sites of metastatic progression, can be integrated with the gene expression-biomarker to better define which treatments are most beneficial for which patients.
  • These studies will be integrated into the STAMPEDE trial protocol such that if successful, the results generated will be considered “level 1” evidence and support clinical implementation of this biomarker for selection of patients for addition of AR-targeting therapies at start of long-term ADT.

What this means to patients: The addition of docetaxel chemotherapy or AR-targeted therapies in men with advanced prostate cancer who are starting long-term ADT can significantly improve outcomes, however is it still unclear which treatment strategy will be most beneficial for an individual patient. Dr. Attard and team will develop a clinical-grade biomarker that will enable the identification of patients who should receive ADT alone vs. ADT + AR-targeted therapy. This project will lead to improved management and outcomes of men with hormone-sensitive prostate cancer.