Could a pill replace chemotherapy for some patients?
In a small Phase II study of early-stage breast cancer patients with BRCA 1 and 2 mutations, researchers found that more than half of women who took the PARP inhibitor talazoparib once daily prior to surgery had no evidence of disease at the time of surgery. If validated in larger trials, the oral medication could replace chemotherapy in these patients.
The trial, which expands on a feasibility study published in mpj Breast Cancer, was presented at the American Society of Clinical Oncology’s annual meeting by Jennifer Litton, M.D., associate professor of Breast Medical Oncology.
“To my knowledge, this study is the first time that a single-agent targeted therapy has shown a pathologic complete response in women with BRCA mutations, including those with triple negative breast cancer,” says Litton.
Mutations in the BRCA 1 and 2 genes account for 5 to 10 percent of all breast cancers, including most hereditary cancers – a population often diagnosed at a younger age – and 10 to 25 percent of triple negative breast cancers, an aggressive type of the disease.
BRCA mutations 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 not only by inhibiting the PARP enzyme, but by trapping the enzyme on DNA to further prevent DNA repair.
While the goal always is to move promising drugs from the metastatic setting to the front line, Litton says previous studies with PARP inhibitors combined with chemotherapies resulted in high rates of toxicities for patients.
“The idea of taking a single pill once a day and having similar – if not better – response rates without the quality-of-life issues women experience with chemotherapy could be tremendous for our patients,” Litton says.