Drug shrinks tumors in clinical trial patients with BRCA-positive breast cancer

In a pilot study of 13 newly diagnosed, BRCA-positive breast cancer patients at MD Anderson, all had their tumors shrink significantly when treated with the drug talazoparib before presurgical chemotherapy.

Tumor shrinkage after two months of treatment with the drug, measured by ultrasound, ranged from 30 to 98%, with an average reduction in tumor volume of 78% among the 13 patients.

“Acknowledging that this is a small study, I can’t think of any systemic therapy that gives results this consistently strong in only two months,” said Jennifer Litton, M.D., associate professor of Breast Medical Oncology and leader of the study. An extension of the trial is underway.

Talazoparib belongs to a class of drugs called PARP inhibitors, which block a DNA repair pathway that tumors can use to survive DNA damage. BRCA1 and BRCA2 are tumor-suppressing genes that, when mutated, account for 5 to 10% of all breast cancers. BRCA-related cancers are thought to be vulnerable to PARP inhibitors.

Litton is principal investigator of an international phase III clinical trial of talazoparib for patients with advanced or metastatic breast cancer. Talazoparib and other PARP inhibitors already have been through phase I safety and phase II/III efficacy clinical trials.

Given these early results for PARP inhibitors, Litton designed a stepwise approach to more quickly move talazoparib into the presurgical treatment setting for patients newly diagnosed with BRCA-positive breast cancer.  She proposed an investigator-initiated pilot study to the drug company, to be supported by MD Anderson’s Moon Shots Program, an ambitious effort to reduce cancer deaths by more rapidly developing and implementing advances in prevention, early detection and treatment based on scientific discoveries.

Litton originally expected the study to take two years to sign up 20 patients. Instead, 13 enrolled in eight months, and the results were striking enough that the study was stopped. Complete results, including pathological response after the full course of treatment through surgery, are being prepared for publication.

An extension of the pilot study opened in August for 20 more patients who will take only talazoparib for six months before proceeding to surgery. Six patients have enrolled. Patients whose disease progresses will proceed to chemotherapy and then surgery.

“If this study produces similarly strong results, the next step would be to directly compare talazoparib to chemotherapy in the presurgical, curative setting,” Litton said. “We might be able to delay or replace chemotherapy if we can get similar efficacy with less toxicity from treatment.”

Read more about the talazoparib trial in MD Anderson’s Newsroom.