PARP inhibitors
- Medical Review: Debu Tripathy, MD
PARP inhibitors are targeted therapies used to treat certain breast, ovarian, pancreatic, and prostate cancers. In breast cancer, PARP inhibitors are FDA approved for people who were born with an inherited BRCA genetic mutation. The breast cancer can be any stage, and must be HER2-negative.
Since the early 2000s, researchers have studied PARP inhibitors as treatments for breast and other cancers. The U.S. Food and Drug Administration first approved a PARP inhibitor to treat ovarian cancer in 2014. Since then, it has approved more PARP inhibitors to treat ovarian and other cancers.
In 2018, the FDA approved the first two PARP inhibitors for metastatic breast cancers caused by an inherited BRCA gene mutation. They are olaparib (Lynparza) and talazoparib (Talzenna). In March 2022, the FDA expanded the approval for olaparib to include high-risk early-stage breast cancers. Researchers continue to study these and other PARP inhibitors in clinical trials.
How PARP inhibitors work
Mutations on certain BRCA genes (BRCA1 or BRCA2) make it harder for cells to repair DNA mistakes that happen when cells divide. If you have an inherited BRCA genetic mutation, it can significantly increase your risk of getting breast cancer.
If a person with an inherited BRCA gene mutation is diagnosed with breast cancer, they are offered different treatments than people without these mutations. Mastectomy is often the recommended surgery. If the cancer is HER2-negative, PARP inhibitors are also recommended.
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 inherited BRCA mutations already have a hard time repairing themselves. PARP inhibitors make it even harder and can cause the cancer cells to die.
PARP inhibitors represent a new option for those with inherited BRCA 1 or 2 mutations, and therefore expand the patient population who should have testing for BRCA mutations to include anyone with metastatic breast cancer or those with early-stage breast cancer who have positive nodes, or still have cancer left at the time of surgery when they receive chemotherapy or hormonal therapy prior to surgery.
Who gets PARP inhibitors
There are two PARP inhibitors approved to treat breast cancer in people with an inherited BRCA genetic mutation: olaparib and talazoparib.
Genetic testing can confirm whether you have an inherited BRCA mutation or other inherited mutations. This testing is done using a blood, saliva, or cheek-swab test.
PARP inhibitors for early-stage breast cancer
Olaparib is FDA approved to treat HER2-negative early-stage breast cancer in people with an inherited BRCA1 or BRCA2 genetic mutation. The cancer must have a high risk of recurrence (coming back).
PARP inhibitors for metastatic breast cancer
Both olaparib and talazoparib are FDA approved to treat HER2-negative metastatic breast cancer in people who have an inherited BRCA1 or BRCA2 genetic mutation.
Getting PARP inhibitors through a clinical trial
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.
Some clinical trials are looking at PARP inhibitors and other therapies for somatic BRCA mutations. Somatic BRCA mutations develop in the genes of the cancer, not in the genes you were born with. Somatic mutations are not inherited. Confirming the cancer has a somatic mutation requires a blood or tissue test that uses next-generation sequencing to look at hundreds of genes in cancer cells.
To find out if you’re eligible for a PARP inhibitor clinical trial, try the Early-stage breast cancer trial search or Metastatic breast cancer trial search tools, visit ClinicalTrials.gov, or talk with your doctor.
How PARP inhibitors are given
Olaparib and talazoparib are pills, as are most PARP inhibitors being studied 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. If you receive a PARP inhibitor through a clinical trial, the dose you receive, when you take it, and whether you also take 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:
- Nausea and vomiting
- Fatigue
- Lung and airway infection or inflammation
- Diarrhea
- Headache
They can also cause low red or white blood cell counts. Low red blood cell counts, called anemia, can lead to fatigue and other problems. Low white blood cell counts, called neutropenia, 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 look for any changes. Sometimes, low blood cell counts can be a sign of a problem with your bone marrow, a type of tissue found inside the bones. Bone marrow problems are not common, but when they do happen, they can be serious.
Lung problems are less common but can be serious side effects of PARP inhibitors. If you have any shortness of breath, coughing or wheezing, or develop a fever, tell your doctor right away so they can keep an eye on the problem.
Tell your doctor about any side effect you notice, 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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