Liquid Biopsy Biomarker Identifies Patients with Improved Response to PARP Inhibition in Metastatic Castrate Resistant Prostate Cancer

CTC Phenotypic Signature Identifies Patients With Improved PARP Inhibitor Responses

November 16, 2016

Epic Sciences announced findings demonstrating a circulating tumor cell (CTC) biomarker can identify patients with metastatic castrate resistant prostate cancer (mCRPC) who are more likely to respond to treatment with a PARP inhibitor in combination with androgen receptor signaling inhibitors (ARSi) compared to those treated with ARSi alone (overall response rate of 93 percent vs. 22 percent). PARP inhibitors are one of the largest classes of new cancer drugs in development and target a type of genomic instability associated with homologous recombination DNA repair deficiency (HRD).

At the 2016 ASCO Annual Meeting, this biomarker was reported by Epic Sciences to identify single HRD-positive (HRD+) CTCs.  In addition, Epic Sciences demonstrated the clinical validity of this biomarker by prognosticating which mCRPC patients would have poor outcomes with ARSi and taxane chemotherapy.  

Today, Epic reports on the further evaluation this biomarker as part of the NCI 9012 study to examine the efficacy of a PARP inhibitor (veliparib) in combination with an ARSi (abiraterone) in patients with mCRPC.

“PARP inhibitors are efficacious in a subset of patients with mCRPC. Therefore, it is critically important to find the patients who will benefit from these novel therapeutics,” said Felix Feng, MD, associate professor of radiation oncology, urology and medicine at UCSF, and lead author of the study.  “Identifying these patients with a simple blood draw represents a tremendous leap forward in the clinical development of PARP inhibitors.” 

The study demonstrated that 29 percent of first-line mCRPC patients were positive for the biomarker, while previous reports identify far fewer patients based on the detection of inactivating HRD mutations associated with PARP inhibitor response from sequencing of single-site, metastatic tissue biopsies (i.e. 13 percent of patients with BRCA2 loss).

In addition to observing increased prevalence within the cohort, the biomarker was used to observe and track dynamic changes in the HRD+ CTCs throughout a patient’s treatment. On average, patients receiving the PARP inhibitor in conjunction with ARSi saw a reduction of HRD+ CTCs during therapy, whereas on average, patients given the ARSi alone saw an increase of HRD+ CTCs while on therapy. 

“This circulating tumor cell biomarker clearly distinguishes a subset of patients who will have poor clinical response on ARSi alone but will have significantly improved responses with PARP inhibition. The biomarker’s higher prevalence has been confirmed in multiple independent cohorts,” said Ryan Dittamore, VP of translational research & clinical affairs at Epic Sciences and co-author on the study.  “We are rapidly accelerating clinical development in partnership with biopharmaceutical companies and academic sponsors to evaluate the biomarker with many novel therapies including PARP inhibitors and other novel HRD-targeting therapies across a range of cancers.”