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Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast
Jennifer K Litton1, J Thaddeus Beck2, Jason M Jones3
1Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC.
Patients And Methods:
Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed.
Results:
Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose).
Conclusions:
Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated.
Clinicaltrials.Gov Identifier:
NCT03499353.
Insights
Neoadjuvant talazoparib showed activity in early-stage triple-negative breast cancer with BRCA mutations. While not meeting all targets, its efficacy was comparable to standard chemotherapy and it was well-tolerated.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Standard neoadjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) with BRCA mutations has uncertain efficacy.
- Biomarker-targeted therapies, like poly(ADP-ribose) polymerase inhibitors, are needed for this patient group.
Purpose of the Study:
- To evaluate the efficacy and safety of neoadjuvant talazoparib in patients with early-stage TNBC and germline BRCA1/2 mutations.
Main Methods:
- A phase II, single-arm, open-label study involving patients with germline BRCA1/2-mutated early-stage TNBC.
- Patients received talazoparib 1 mg daily for 24 weeks, followed by surgery. Primary endpoint was pathologic complete response (pCR).
Main Results:
- The pCR rate was 45.8% in the evaluable population and 49.2% in the intent-to-treat (ITT) population.
- Treatment-related adverse events included anemia (39.3%) and neutropenia (9.8%). Quality of life was not significantly impacted.
- pCR rates were comparable to anthracycline- and taxane-based chemotherapy regimens.
Conclusions:
- Neoadjuvant talazoparib monotherapy demonstrated activity in this patient population.
- Talazoparib was generally well-tolerated, suggesting potential as a targeted treatment option.
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