Single-Agent Talazoparib Shows Activity in the Neoadjuvant Treatment of Triple-Negative Breast Cancer

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For the neoadjuvant treatment of triple-negative breast cancer, the oral poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib yielded promising pathologic complete response rates in the phase II single-arm NEOTALA trial presented at the 2021 ASCO Annual Meeting.1

Preoperative chemotherapy is standard therapy for most early-stage triple-negative breast cancer. Talazoparib is the first single-agent targeted drug to achieve pathologic complete responses in germline BRCA-positive HER2-negative patients with early breast cancer, including triple-negative disease, according to Jennifer Keating Litton, MD, Vice President of Clinical Research and Professor of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center.

Jennifer Keating Litton, MD

Jennifer Keating Litton, MD


Treatment with talazoparib resulted in pathologic complete responses in 45.8% of 48 evaluable patients and 49.2% of the intention-to-treat population of 61 patients. Event-free survival and overall survival have not yet been reached, Dr. Litton reported.

“Talazoparib monotherapy was active in the neoadjuvant setting and showed pathologic complete response rates comparable to those historically observed with combination anthracycline- and taxane-based chemotherapy regimens,” Dr. Litton said. “The findings could signal the emergence of a non–chemotherapy-based neoadjuvant option for patients with this aggressive breast cancer subtype.”


The open-label single-arm study evaluated talazoparib at 1 mg/d in 61 patients with stage I to III HER2-negative, ER/PR–negative breast cancer and germline BRCA1/2 mutations. Most women (90%) remained on talazoparib for at least 20 weeks, and 74% received the drug for the full 24-week study period. The primary endpoint was pathologic complete response rate by independent review in the evaluable population, which included patients who received at least 80% of the talazoparib dose and underwent surgery and assessment, plus patients who experienced disease progression before response could be assessed.


  • The phase II single-arm open-label NEOTALA trial evaluated the PARP inhibitor talazoparib as neoadjuvant therapy for early triple-negative breast cancer. All patients had BRCA mutations.
  • The response rate was 45.8% in the evaluable population and 49.2% in the intention-to-treat population.
  • The rates are comparable to those achieved with polychemotherapy.

The investigators also looked at residual cancer burden (RCB), a four-category index derived from primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. In the evaluable population, approximately 46% of patients had RCB0 and 31% had RCBII (moderate burden). No patients had RCBI (minimal burden) or RCBIII (extensive burden), and 23% had RCB “other,” which included patients who experienced disease progression on study and those who lacked surgery or assessment.

Talazoparib was generally well tolerated, and treatment-emergent adverse events were consistent with the established safety profile, with mostly grade 1 or 2 fatigue, nausea, and alopecia. Grade 3 events were observed in 43%; one grade 4 event occurred, which was decreased neutrophil count. Grade 3 anemia, a known toxicity associated with this drug, was observed in 39% of patients. 

DISCLOSURE: Dr. Litton has received honoraria from UpToDate; has served as a consultant or advisor to AstraZeneca, Ayala Pharmaceuticals, Medivation/Pfizer, and Pfizer; has participated in a speakers bureau for Clinical Care Options, Med Learning Group, Medpage, Medscape, Physician Education Resource, Prime Oncology, and UpToDate; has received institutional research funding from AstraZeneca, EMD Serono, Genentech, GlaxoSmithKline, Merck, Pfizer, and Zenith Epigenetics; holds intellectual property in UpToDate; has been reimbursed for travel, accommodations, or other expenses by Clinical Care Options, Med Learning Group, Medscape, and Physician Education Resource; and has held other relationships with Pfizer/Medivation.


1. Litton JK, Beck JT, Jones JM, et al: Neoadjuvant talazoparib in patients with germline BRCA1/2 mutation-positive HER2-negative breast cancer: Results of a phase 2 study. 2021 ASCO Annual Meeting. Abstract 505. Presented June 6, 2021.

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