New Drugs, PARP Inhibitors

            The following article was adapted from the website of Living Beyond Breast Cancer (LBBC). This is an organization based in Philadelphia, therefore it describes the US situation.  However, there are clinical trials at Kingston General Hospital with PARP inhibitors for women with mutations in their brca genes and metastatic breast cancer.  Because these drugs are new, it was decided to include only women with ER+, Her2 negative or triple-negative breast cancer.

Since the article was published, clinical trials are being designed with PARP inhibitors for women without mutations in brca genes. For more details, ask your oncologist.  

https://www.lbbc.org/learn/treatments-and-research/targeted-therapy/parp-inhibitors-brca-positive-breast-cancer

PARP Inhibitors for BRCA-mutation Positive Breast Cancer

UPDATED 

OCTOBER 31, 2018

REVIEWED BY: 

Debu Tripathy, MD

            PARP inhibitors are targeted therapies used to treat people who were born with a mutation on the BRCA genes. These mutations increase the risk of breast cancer but also ovarian and prostate cancer and melanoma. 

            In 2014 the U.S. Food and Drug Administration (FDA) approved a PARP inhibitor to treat ovarian cancer and has approved more PARP inhibitors to treat ovarian cancer since then. The results were encouraging, for this reason in 2018 the FDA approved the first two PARP inhibitors for metastatic breast cancers with a BRCA gene mutation. They are olaparib (Lynparza) and talazoparib (Talzenna). Researchers are studying other PARP inhibitors in clinical trials.

How PARP Inhibitors Work

            Mutations on the BRCA1 or BRCA2 genes make it harder for cells to repair DNA mistakes that happen when cells divide. This can significantly increase your risk of getting breast cancer.

            PARP inhibitors stop an enzyme in the body, known as poly (ADP-ribose) polymerase, or PARP, from repairing cancer cell DNA. Cancer cells in people with BRCA mutations already have a hard time repairing their DNA. PARP inhibitors make it even harder, and the absence of DNA repair can cause the cancer cells to die.

Who Gets PARP Inhibitors

            There are two PARP inhibitors approved to treat breast cancer, olaparib and talazoparib. These medicines may be an option if three conditions apply:

            Other PARP inhibitors, including niraparib, rucaparib and veliparib, have not yet been FDA approved for breast cancer. They may be available through clinical trials, most of which are for people with metastatic breast cancer. To find out if you’re eligible for a PARP inhibitor clinical trial, visit ClinicalTrials.gov and talk to your doctor.  

The only way to know if you were born with a BRCA mutation is to get genetic testing. This testing is done using a blood, saliva or cheek-swab test, that is on normal cells (not the cancer).  The cancer cells however accumulate many mutations that are new, ie did not exist in the DNA of your normal tissues. These are called “somatic” mutations, and the testing has to be done on a sample of your tumor.

How PARP Inhibitors Are Given

            Olaparib and talazoparib are pills, as are most PARP inhibitors in clinical trials. Olaparib is usually taken twice every day, at least 12 hours apart, with or without food. Talazoparib is taken once each day, also with or without food. How often and at what dose you take a PARP inhibitor as part of a clinical trial, and whether you get it along with other anti-cancer medicines, will depend on the design of the study.

PARP Inhibitor Side Effects

In general, PARP inhibitors cause fewer and less serious side effects than some other cancer treatments.  The most common side effects of PARP inhibitors are:

They can also cause low red blood cell counts, called anemia, which can lead to fatigue and other problems; and low white blood cell counts, called neutropenia, which can increase your risk of infection. Your doctor will check your blood counts through blood tests before you start taking a PARP inhibitor and throughout your treatment to check for any changes. Sometimes, low blood cell counts can be a sign of a problem with your bone marrow, a soft tissue found inside the bones. Bone marrow problems are not common but when they do happen, they can be serious.

            Other serious but less common side effects of PARP inhibitors are problems with the lungs. If you have any shortness of breath, coughing or wheezing, or get a fever, tell your doctor right away so he or she can keep an eye on the problem.

Tell your doctor about any side effect you have, even when it seems mild. Your doctor may be able to give you medicine to treat the side effect or suggest lifestyle changes that could help manage it. If side effects are serious or impact your everyday life, your doctor may lower your dose, recommend a treatment break or switch you to a different medicine.

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