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PARP Inhibitors and Hereditary Cancer: What’s New?

April 12, 2018

PARP Inhibitors and Hereditary Cancer: What’s New?

by Sue Friedman

PARP inhibitors are drugs designed specifically to treat cancers in people with certain inherited mutations, including BRCA1 and BRCA2, among others. These drugs block an enzyme – known as PARP – used by cells to repair damage to their DNA. Although these agents seem to be most effective in people with mutations—not just BRCA but also ATM, PALB2 and others—PARP inhibitors can also treat some cancers in people without mutations. Because these drugs target only cancer cells they generally have fewer side effects than chemotherapy.

PARP inhibitors were first introduced in clinical trials in 2005. FORCE has been following the progress of these drugs since then. We have played a major role in recruiting patients with hereditary cancer for clinical studies that led to FDA approval of Lynparza (olaparib), Rubraca (rucaparib), and Zejula (niraparib). Two others – Talazoparib and Veliparib – are being actively studied, but have not yet received FDA approval. Here’s our update on PARP inhibitors in clinical care and research.

First FDA Approval for Metastatic Breast Cancer!

This year began on a positive note, with the first FDA approval of a PARP inhibitor for treating breast cancer. Lynparza received FDA approval to treat metastatic breast cancer in people with BRCA mutations. BRACAnalysis CDx—a companion diagnostic test—received approval at the same time. The National Comprehensive Cancer Network (NCCN) lists Lynparza as a preferred treatment for women with advanced breast cancer and a BRCA mutation.

Breast Cancer Research

In December 2018, results from the EMBRACA study—a large clinical trial for metastatic breast cancer—were reported at the San Antonio Breast Cancer Symposium. Patients who received Talazoparib had a longer period of time before their cancer worsened, compared to patients who did not receive the drug. Experts are hopeful that Talazoparib also will receive FDA approval this year to treat metastatic breast cancer caused by a BRCA mutation.

Veliparib is another PARP inhibitor that is being studied for treatment of metastatic triple-negative breast cancer, as well as metastatic breast cancer in people with a BRCA mutation.

Researchers are also studying PARP inhibitor effectiveness against breast cancer in other scenarios, including:

  • patients with metastatic breast cancer who have inherited mutations other than BRCA, such as ATM and PALB2
  • patients with triple-negative metastatic breast cancer, without an inherited mutation
  • PARP inhibitors in combination with other agents, such as immunotherapies
  • patients with earlier stages of breast cancer

Visit our new Research Search Tool to find PARP inhibitor research studies enrolling patients with breast cancer.

Advanced Ovarian Cancer

Two PARP inhibitors—Lynparza (olaparib) and Rubraca (rucaparib)—have received FDA approval to treat advanced, recurrent ovarian, fallopian tube, and primary peritoneal cancer. Each has a slightly different indication, but both are approved for women with a BRCA mutation.

Ovarian Cancer Maintenance Therapy

Maintenance therapy is a type of treatment that is given after initial standard treatment has been completed to try to keep the cancer from returning. Lynparza, Zejula, and Rubraca have all received FDA approval for use as maintenance therapy in women with ovarian, fallopian tube, and primary peritoneal cancer (regardless of their BRCA status).

Ovarian Cancer Research

Researchers are studying PARP inhibitor effectiveness when used in combination with other agents, including immunotherapies and with drugs that shrink blood supply.  Visit our Research Study Search Tool to find clinical trials enrolling patients with hereditary ovarian, fallopian tube, and primary peritoneal cancer.

Pancreatic Cancer Research

Although the FDA has not approved any PARP inhibitors for treating pancreatic cancer, several are being actively studied. Veliparib is being studied in this clinical trial recruiting people with a BRCA1, BRCA2 or PALB2 mutation. The POLO Study is a pancreatic cancer maintenance treatment clinical trial investigating the PARP inhibitor, Lynparza. Another clinical trial is looking at Rubraca to treat people with a BRCA1, BRCA2, or PALB2.

Visit our Research Study Search Tool to find additional pancreatic cancer treatment clinical trails.

Prostate Cancer Research

PARP inhibitors are not currently FDA-approved for treating prostate cancer. However, clinical trials are studying Lynparza, Rubraca, and Talazoparib to treat men with advanced prostate cancer associated with an inherited mutation in BRCA, CHEK2, ATM, PALB2 and other genes, as well as men who test negative for inherited mutations. As part of these clinical trials, tumor tests look at gene mutations within the tumor (somatic mutations) to predict whether the prostate cancer is likely to respond to a PARP inhibitor or some other treatment. Visit our Research Study Search Tool to find PARP inhibitor studies enrolling patients with prostate cancer.

FORCE continues to play a role in PARP inhibitor research and educating the community on their use in clinical care. We are hopeful that current research will lead to additional FDA approval of these drugs.

Posted in: Research , Cancer Treatment
Tags: BRCA , Ovarian Cancer , Genetic Testing , BRCA1 , BRCA2 , PALB2 , Pancreatic Cancer , ATM , Gene Panel Testing , Metastatic Breast Cancer , Ovarian Cancer Treatment , PARP Inhibitor , Cancer Research , Advanced Breast Cancer , Inherited Mutations , Prostate Cancer Treatment , Metastatic Prostate Cancer , Cancer Targeted Therapy

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