Expanding access to PARP inhibitors in prostate cancer treatment

Last month, Myriad attended the 2023 ASCO Genitourinary Cancers Symposium (ASCO GU) to connect with researchers and doctors around emergent and controversial areas in the treatment of prostate cancer. Discussions included AI guided biopsies, active surveillance versus definitive treatment in favorable intermediate risk patients, and most notably PARP inhibitors.

PARP inhibitors are a type of therapy that targets the DNA repair pathway, which plays a critical role in maintaining the integrity of the genome. In cancer, the DNA repair pathway is essential for keeping those cells alive. By inhibiting the DNA repair pathway, PARP inhibitors cause cancer cells to accumulate too much DNA damage and undergo cell death.

PARP inhibitors have shown promise in the treatment of several types of cancer, including ovarian, breast, pancreatic and prostate cancer, particularly in patients with mutations in genes involved in DNA repair, such as BRCA1 and BRCA2.

In a 2020 study published in The New England Journal of Medicine, results showed men with metastatic castration-resistant prostate cancer (mCRPC) on a novel hormone treatment experienced significant, clinical improvement from Olaparib (a PARP inhibitor) in radiographic-progression-free survival compared to men on novel hormone treatment alone. The patient populations shared mutations in BRCA1, BRCA2, ATM and/or other HRR genes. The subjects receiving Olaparib also trended toward an average improved overall survival of 18 months compared to an average of 14.7 months in the other cohorts. 

Olaparib was approved by the FDA in 2020 for adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC patients who have progressed following treatment with enzalutamide or abiraterone.

In a separate 2018 study, Rucaparib, another PARP inhibitor, was evaluated in mCRPC patients with a deleterious germline and/or somatic alteration in BRCA1, BRCA2, ATM and other HRR genes.

PARP inhibitors are often used in combination with other treatments, such as hormone therapy or chemotherapy, to further improve patient outcomes; however, patients can only access these novel therapies by having an eligible gene mutation.

Myriad’s UroSuite™ offers MyRisk® Hereditary Cancer Testing and Precise™ Tumor, a germline and somatic test respectively. Germline mutations are unchanging mutations inherited from parents and found in every cell in the body, whereas somatic mutations are acquired, confined to the tumor and change over time.

MyRisk offers a multi-gene panel that examines a patient’s gene status to determine if a patient’s tumor may be appropriate for clinical trials or novel therapies such as PARP inhibitors. 

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend both germline and somatic testing for patients with metastatic prostate cancer. By combining both germline and somatic testing, there is a doubled chance of finding clinically actionable alterations, since tumor testing alone cannot identify large rearrangements.

For more information on UroSuite™ and how it can offer comprehensive testing across the spectrum of prostate cancer care, along with best-in-class support and specialists, click here: Providers.