PARP inhibitor improves progression-free survival in patients with advanced breast cancers and BRCA

December 8, 2017, University of Texas M. D. Anderson Cancer Center

In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over available chemotherapies for patients with metastatic HER2-negative breast cancer and mutations in the BRCA1/2 genes.

The results of the EMBRACA trial were presented today at the 2017 San Antonio Breast Cancer Symposium by Jennifer Litton, M.D., associate professor of Breast Medical Oncology.

"The trial found that talazoparib provides a significant clinical benefit to all patient subgroups, including those with hormone receptor-positive and triple-negative disease," said Litton. "The results of this trial are quite exciting and indicate talazoparib is a novel treatment option for patients with metastatic and BRCA mutations."

Current therapies for metastatic include sequential hormonal therapies and chemotherapies, but there are no approved therapies specifically for patients with and a known BRCA mutation, explained Litton.

Mutations in the BRCA1/2 genes, which account for 5 to 10 percent of all breast cancers, cause defects in normal DNA damage repair. PARP inhibitors block an additional DNA repair pathway, and the anti-tumor effects of PARP inhibitors can be intensified in patients with BRCA mutations. Talazoparib works by not only inhibiting the PARP enzyme, but by trapping the enzyme on DNA to further prevent DNA repair.

To date, no PARP inhibitors have been approved by the Food and Drug Administration to treat breast cancers, although three previously have been approved for the treatment of certain patients with ovarian cancers.

EMBRACA is an international, Phase III clinical trial enrolled 431 patients with locally advanced or metastatic and hereditary BRCA1/2 gene mutations. Patients with HER2-positive disease were excluded as there are approved targeted therapies for those cancers. Patients could have had up to three previous chemotherapies, including platinum-based therapies.

Participants were randomized 2:1 to receive either talazoparib (287) or physician's choice of treatment (PCT) of single-agent therapy (144), either capecitabine, eribulin, gemcitabine or vinorelbine. Fifty-four percent of participants had HR+ disease and 46 percent had TN cancer; BRCA1 and BRCA2 mutations were split at 45 and 55 percent, respectively.

"Importantly, the trial met its primary endpoint of progression-free survival. Patients were nearly 46 percent less likely to have progressed on talazoparib compared to physician's choice," said Litton. "Secondary endpoints also were promising, including a dramatic improvement in time to clinical deterioration among patients receiving talazoparib."

The median PFS, assessed by blinded independent review, was 8.6 months in the talazoparib arm, compared with 5.6 months in the PCT arm, a statistically significant improvement. The overall response rate, or percentage of patients with tumor shrinkage, was 62.6 percent and 27.2 percent in the talazoparib and PCT arms, respectively. Twelve participants had complete responses, all in the talazoparib arm.

Patient-reported quality-of-life measures revealed a prolonged time to deterioration of overall health, 24.3 months in the talazoparib arm compared to 6.3 months for the PCT arm.

Grade 3-4 hematological adverse events occurred in 55 percent of patients receiving talazoparib and 39 percent of those on chemotherapy, but talazoparib was associated with fewer high-grade non-hematological events, including gastrointestinal and skin/subcutaneous tissue disorders. Grade 3-4 serious events occurred in 26 and 25 percent of patients receiving talazoparib and PCT, respectively. Adverse events resulting in death occurred in 2.1 percent of patients on talazoparib and 3.2 percent on PCT.

The study also will report overall survival, though the data are immature at this point and will continue to be monitored.

"It is encouraging to see this oral PARP inhibitor was well-tolerated and superior to chemotherapy alone. We look forward to seeing how overall survival is affected, but I think talazoparib will be an excellent option for patients with metastatic disease and BRCA mutations," said Litton.

Litton hopes to continue investigating the utility of PARP inhibitors in additional with BRCA mutations, including those with early-stage disease, as well as possibilities for enhancing the activity of PARP inhibitors in without inherited BRCA .

Explore further: PARP inhibitor may be effective against some TNBC lacking BRCA mutations

Related Stories

PARP inhibitor may be effective against some TNBC lacking BRCA mutations

November 1, 2017
The investigational PARP inhibitor talazoparib caused regression of patient-derived xenografts (PDXs) of triple-negative breast cancers (TNBC) that had BRCA mutations and also those that did not have BRCA mutations but had ...

Frontline PARP inhibitor shrinks tumors in BRCA-positive breast patients

October 5, 2016
All 13 newly diagnosed breast cancer patients with BRCA mutations had their tumors shrink significantly when treated with a PARP inhibitor ahead of frontline presurgical chemotherapy in a pilot study at The University of ...

Adding Veliparib to chemotherapy improved response rates among patients with BRCA-mutant breast cancer

December 8, 2016
Adding the investigational poly(ADP-ribose) polymerase (PARP) inhibitor veliparib to carboplatin and paclitaxel chemotherapy improved the overall response rate without increasing adverse events among patients who had locally ...

Olaparib slows growth of BRCA-related metastatic breast cancer

June 5, 2017
Findings from a phase III clinical trial of about 300 women may introduce PARP inhibitors as a new type of treatment for breast cancer. Compared to standard chemotherapy, the oral targeted medicine olaparib (Lynparza) reduced ...

Drug combination boost PARP inhibitor response in resistant ovarian cancer

April 3, 2017
About one-third of patients with ovarian cancer who wouldn't be expected to respond to a PARP inhibitor had partial shrinkage of their tumor when a kinase inhibitor was added to treatment, report scientists from Dana-Farber ...

Rucaparib boosts progression-free survival in BRCA mutant recurrent ovarian cancer

September 8, 2017
Rucaparib maintenance therapy increases progression-free survival in BRCA mutant recurrent ovarian cancer by 77%, according to late-breaking results from the ARIEL3 trial reported today at the ESMO 2017 Congress in Madrid.

Recommended for you

Some brain tumors may respond to immunotherapy, new study suggests

December 10, 2018
Immunotherapy has proved effective in treating a number of cancers, but brain tumors have remained stubbornly resistant. Now, a new study suggests that a slow-growing brain tumor arising in patients affected by neurofibromatosis ...

A code for reprogramming immune sentinels

December 10, 2018
For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering ...

Study finds higher risk of breast cancer for women after giving birth

December 10, 2018
Younger women who have recently had a child may have a higher risk of breast cancer than their peers of the same age who do not have children, according to a large-scale analysis co-led by a University of North Carolina Lineberger ...

Researchers develop personalized medicine tool for inherited colorectal cancer syndrome

December 10, 2018
An international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes ...

Study shows key enzyme linked to therapy resistance in deadly lung cancer

December 10, 2018
Researchers at The University of Texas MD Anderson Cancer Center have identified a link between an enzyme tied to cancer formation and therapy resistance in patients with epidermal growth factor receptor (EGFR)-mutant non-small ...

Potential seen for tailoring treatment for acute myeloid leukemia

December 8, 2018
Advances in rapid screening of leukemia cells for drug susceptibility and resistance are bringing scientists closer to patient-tailored treatment for acute myeloid leukemia (AML).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.