Principal Investigators:
Veda Giri, MD (Thomas Jefferson University)
Susan Halabi, PhD (Duke University)
Alexander Wyatt, PhD (University of British Columbia)

Co-Investigators: Rhonda Bitting, MD (Duke University), Christopher McNair, PhD (Thomas Jefferson University)

Description: 

• 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.

What this means to patients: Dr. Giri and team will create a large international registry of data from patients treated with various PARP inhibitors in order to develop a better understanding of how different 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.