The Prostate Cancer Foundation (PCF) recently announced the 2020 Class of PCF Team Challenge Awards including the Project “PARPi Response Evaluation for Clinical Impact and Scientific Innovation in Oncology: The PRECISION Registry.” Team leaders for this award include: Veda Giri, MD (Thomas Jefferson University), Susan Halabi, PhD (Duke University), and Alexander Wyatt, PhD (University of British Columbia). Co-Investigators include: Rhonda Bitting, MD (Duke University), and Christopher McNair, PhD (Thomas Jefferson University). This is the fourth Challenge Award that Dr. Halabi has received from PCF as a PI.
PCF Challenge Awards fund international, multi-institutional, cross-disciplinary teams of investigators conducting highly innovative research with the greatest potential for accelerating new and improved treatments for advanced prostate cancer. Following a rigorous peer review process that assessed each project’s scientific merit and potential patient impact, 12 highly coveted PCF Challenge Awards totaling $11 million were granted to teams at some of the world’s leading cancer research institutions.
This project will create a large international registry of data from patients treated with various PARP inhibitors to better understand how genomic alterations render sensitivity or resistance to these treatments. This will result in improved clinical use of these treatments and lead to new therapeutic strategies for patients with prostate cancer. This project includes:
- The PARP inhibitors olaparib and rucaparib are a new class of “precision medicines” that have recently been FDA-approved for metastatic castration-resistant prostate cancer (mCRPC) patients whose tumors have mutations in certain DNA repair genes. These include mutations that were either inherited (“germline”) or acquired in the tumor (“somatic”) in BRCA1, BRCA2, ATM, PALB2, CHEK2, and multiple other genes. Several additional PARP inhibitors are also being tested in clinical trials.
- However, inconsistent response rates, response durations, and magnitudes of response to PARP inhibitors have been seen in patients with different DNA repair gene mutations. For instance, 83% of patients with BRCA1/2 mutations respond, compared to 37% of patients with ATM Larger datasets spanning diverse practice and patient settings are needed to improve and generalize appropriate use of PARP inhibitors in patients with mCRPC.
- Veda Giri and team are developing “The PRECISION Registry,” an international, collaborative registry of clinical, genomic, and outcomes data from patients with DNA repair mutations who have been treated with PARP inhibitors. Data sources will include pharmaceutical company clinical trial data, off-study data from academic and clinical practices, non-pharmaceutical company trials, prostate cancer registries, and the Durham VA.
- This registry will be used to conduct a meta-analysis to collectively assess responses to PARP inhibitors in patients with different DNA repair gene mutations.
- Bioinformatics and genomic analyses will be conducted using genomic sequencing data to identify genomic modifiers and biomarkers of PARP inhibitor responses.
- If successful, this project will greatly improve clinical use of PARP inhibitors in patients with mCRPC, inform strategies to enhance responses to PARP inhibitors, and accelerate the development of new therapeutics and clinical trials.
For more information and description about this Award, please go the PCF website.