Talazoparib Yields Significant Pathologic Complete Response in gBRCA-Positive, Operable Breast Cancer

In a study of patients with gBRCA-positive, operable breast cancer, single-agent talazoparib produced a significant complete response with manageable toxicity (J Clin Oncol. 2019 Aug 28. Epub ahead of print).

“This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (gBRCA-positive) and operable breast cancer,” explained Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, and co-investigators.

The study enrolled 20 patients, with a median age of 38 years, from August 2016 to September 2017. To be eligible, patients had to have stage I to III breast cancer, with a ≥1 cm invasive tumor, and gBRCA-positive disease. Most patients (n = 12) had stage I disease, 5 had stage II disease, and 3 had stage III disease.

The majority of patients (n = 16) were gBRCA1-positive and 4 were gBRCA2-positive. There were 15 patients with triple-negative breast cancer, and 5 had hormone receptor-positive disease.  

Patients underwent pretreatment biopsy, and received talazoparib 1 mg daily for 6 cycles of 28 days, and then had surgery. Adjuvant therapy was administered at the physician’s discretion. The main end point of the study was residual cancer burden (RCB). The pathologic complete response rate for RCB-0 was 53%, and RCB-0/1 had a response rate of 63%. One patient received chemotherapy before surgery and was not included in RCB analysis.

The most common adverse event, experienced by 8 (40%) patients, was grade 3 anemia that required transfusion. Grade 3 and 4 toxicities included neutropenia and thrombocytopenia. Nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea were common grade 1 or 2 toxicities. 

“Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity,” concluded Dr Litton and colleagues. The significant response to treatment observed here supports the larger, ongoing phase 2 trial.—Kaitlyn Manasterski