In a study reported in the Journal of Clinical Oncology, Jennifer K. Litton, MD, and colleagues found that 6 months of neoadjuvant talazoparib therapy resulted in a high rate of residual cancer burden (RCB) of 0 (pathologic complete response) in patients with stage I–III breast cancer with germline pathogenic BRCA mutations.
Jennifer K. Litton, MD
Study Details
In the study, 20 patients enrolled between August 2016 and September 2017 received 6 months of once daily oral talazoparib (1 mg), followed by definitive surgery. Patients had to have 1 centimeter or larger invasive tumors. Patients with HER2-positive tumors were excluded. Patients had a median age of 38 years; 16 were BRCA1- and 4 were BRCA2-positive; 15 had triple-negative disease and 5 had hormone receptor (HR)-positive disease; disease stage was I in 5 patients, II in 12, and III in 3.
The primary endpoint was RCB (using the MD Anderson RCB Calculator).
Responses
Among the 20 patients, 1 chose to receive chemotherapy before surgery after 5 months of neoadjuvant talazoparib and was not included in the RCB analysis. The 19 remaining patients completed 6 months of neoadjuvant talazoparib.
Among the 19 evaluable patients, 10 (53%) had RCB-0 (pathologic complete response) and 12 (63%) had RCB-0/I. RCB-II and RCB-III were found in five and three patients, respectively. RCB-0/I responses were observed in 53% of patients with a BRCA1 mutation, all patients with a BRCA2 mutation, 57% of patients with triple-negative disease, 80% of patients with HR-positive disease, 83% of patients with T1 tumors, and 54% of patients with ≥ T2 tumors.
KEY POINTS
- 6 months of therapy with neoadjuvant talazoparib was associated with a 53% RCB-0 rate.
- High RCB-0/I rates were observed across disease subgroups.
Adverse Events
The most common nonhematologic adverse events of any grade among the 20 patients who received treatment were nausea (75%), fatigue (70%), alopecia (55%), and dizziness (30%); a grade 3 adverse event (urinary tract infection) was observed in one patient. Grade 3 or 4 hematologic adverse events consisted of anemia (40%, all grade 3, with all eight patients requiring transfusion), neutropenia (15%, all grade 3), and grade 4 thrombocytopenia (one patient). Dose reductions were required in 45% of patients.
The investigators concluded, “Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports [a] larger, ongoing neoadjuvant trial.”
Jennifer K. Litton, MD, of the Department of Breast Medical Oncology, Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the MD Anderson Moonshots Program, Toomim Family Fund, National Cancer Institute, Biomarin, and Medivation/Pfizer. For full disclosures of the study authors, visit jco.ascopubs.org.
