FDA approves talazoparib for some BRCA-positive metastatic or locally advanced breast cancers

The U.S. Food and Drug Administration approved the PARP inhibitor talazoparib (Talzenna) to treat metastatic or locally advanced HER2-negative breast cancer in people with inherited BRCA mutations. Metastatic breast cancer is cancer that spread to distant parts of the body, like the lungs, liver, bones, or brain. When a breast cancer is locally advanced, it has grown large in the breast or has spread from where it started in the breast to nearby tissue or lymph nodes but not to distant parts of the body.

This approval was based on findings from EMBRACA, a phase III clinical trial that compared treatment with talazoparib to treatment with standard chemotherapies. Those who took talazoparib had longer progression-free survival, the length of time until a cancer grows or spreads, than peers treated with chemotherapy.

The cancer only has to be HER2-negative, which means this PARP inhibitor may offer a new treatment option for people with triple-negative disease or hormone receptor-positive, HER2-negative disease.

Background

Everyone has BRCA genes, but some people inherit mutations, or errors, in those genes from their mother or father that make developing breast cancer more likely. The most common breast cancer-related gene mutations are found in the BRCA1 and BRCA2 genes.

Talazoparib is the second PARP inhibitor to be approved to treat breast cancer in people with BRCA mutations. The first was olaparib (Lynparza), which was approved in early 2018. PARP inhibitors stop the PARP enzyme from repairing cancer cell DNA. BRCA mutations already make it hard for cancer cells to repair their DNA. By using PARP inhibitors, repair becomes even more difficult, and can cause the cancer cells to die.

The EMBRACA trial findings

The FDA approval was based on the findings of EMBRACA, a phase III, open-label clinical trial. In open-label trials, both the participants and the researchers know which treatment the participant receives.

Participants in EMBRACA had locally advanced or metastatic HER2-negative breast cancer and up to three past courses of chemotherapy for either early-stage or metastatic breast cancer. All had known or suspected inherited BRCA mutations. LBBC reported on EMBRACA when it was presented at the 2017 San Antonio Breast Cancer Symposium.

The trial included 431 participants who were randomly put into one of two groups:

• 281 participants took a talazoparib pill once a day.
• 144 participants were treated with their doctor’s choice of the standard chemotherapies capecitabine (Xeloda), eribulin (Halaven), gemcitabine (Gemzar) or vinorelbine (Navelbine).

The researchers found that participants in the talazoparib group went longer without the cancer growing or spreading, called progression-free survival. The median progression-free survival was

• 8.6 months for people taking talazoparib
• 5.6 months for people taking their doctor’s choice of chemotherapy

It was too soon to fully understand the differences in overall survival, which is how long participants lived after joining the trial until death from any cause.

Talazoparib side effects

The chances of serious side effects were similar between the study groups, but slightly more common for people taking talazoparib than for those taking chemotherapy. Serious side effects occurred in

• 31.8 percent for the talazoparib group
• 29.4 percent for the chemotherapy group

Common side effects were:

• anemia
• fatigue
• nausea

Even though more people in the talazoparib group had serious side effects, more people in the chemotherapy group chose to leave the study due to side effects of treatment.

What this means for you

As the second approved PARP inhibitor for breast cancer, talazoparib offers another treatment option for people with metastatic HER2-negative breast cancer who have a BRCA mutation. If you have hormone receptor-positive, HER2-negative breast cancer, or triple-negative breast cancer, it may give you another treatment option. It may allow you to try a different class of medicine even if you had cancer growth while taking chemotherapy.

Researchers are still studying PARP inhibitors to track whether they lengthen life.

Before you are given talazoparib, you must get a test showing you carry a BRCA gene mutation. The FDA also approved BRACAnalysis CDx, a genetic test, to help figure out if you are eligible for talazoparib. Without insurance, talazoparib costs around $14,580 per month, or about $174,960 per year.

Read more about metastatic breast cancer and genetics and family risk here.

Litton, J, Rugo, H, Ettl, J, et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. New England Journal of Medicine. 2018 379 (8), 753-763