In patients with germline BRCA1/2 (gBRcA1/2) mutation-positive early human epidermal growth factor receptor 2 (HER2)-negative breast cancer, neoadjuvant talazoparib demonstrated activity and pathologic complete response (pCR) rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens, according to study results presented by Jennifer Keating Litton, MD, of The University of Texas MD Anderson Cancer Center in Houston, during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Dr Litton stated that talazoparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor is approved as monotherapy for the treatment of adult patients with gBRCA1/2-mutated HER2-negative locally advanced or metastatic breast cancer and is generally well tolerated.

The germline BRCA1/2 mutations, she noted, that are found in the tumors of 9% to 15% of patients with triple-negative breast cancer, rely on PARP for DNA repair. Dr Litton and colleagues evaluated the efficacy and safety of talazoparib in the neoadjuvant setting in a phase 2, nonrandomized, single-arm, open-label study (ClinicalTrials.gov Identifier: NCT03499353). The primary endpoint of the trial was pCR as assessed by Independent Central Review (ICR) after 24 weeks of completed talazoparib monotherapy (1 mg/day [0.75 mg for moderate renal impairment]) followed by surgery. pCR by investigator assessment (INV) and residual cancer burden (RCB) by ICR (with 0=pCR, I=minimal, II=moderate, III=extensive) were secondary endpoints. The evaluable population (48 patients) included those who received at least 80% of the talazoparib dose prescribed at treatment start and underwent breast surgery and pCR assessment, plus those who progressed before pCR could be assessed. The intention-to-treat (ITT) population (61 patients) included all patients who received at least 1 dose of talazoparib.


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The mean patient age was 44.6 years. All patients had triple-negative breast cancer, Dr Litton explained, and adenocarcinoma was present in 60 patients and 1 patient had squamous cell histology. Twenty patients had stage I disease, 27 patients had stage II, and 14 patients had stage III. Mean duration of treatment was 23.3 weeks (initiated a mean of 4.5 weeks after disease onset). The mean overall relative dose intensity was 84.5% in the ITT population (9 patients received less than 80% of the prescribed dose), with 10 patients (16.4%) discontinuing treatment due to progressive disease, 1 patient experienced treatment disruption due to COVID-19 restrictions, and 2 disrupted treatment for other reasons.

For the evaluable population, Dr Litton reported, the pCR rate by ICR was 45.8% (95% CI, 32.0-60.6) and by INV was also 45.8% (95% CI, 32.0-60.6). The RCB 0 rate by ICR was 45.8%, the RCB I rate was 0%, the RCB II rate was 31.3% and the RCB III rate was 0%. The corresponding pCR rates in the ITT population were 49.2% (95% CI, 36.7-61.6) by ICR, and 47.5% (95% CI, 35.0-60.1) by INV. The ITT RCB rates were 30% for RCB 0, 1.6% for RBC I, 27.9% for RCB II, and 0% for RCB III.

Among treatment-related adverse events (TRAEs), which were reported in 98.4% of patients overall, fatigue was most common (77.0%; grade 1, 55.7%; grade 2, 19.7%; grade 3, 1.6%), with nausea (63.9%; grade 1, 50.8%; grade 2, 13.1%; grade 3, 1.6%), and alopecia (57.4%; grade 1, 54.1%; grade 2/3 11.5%; grade 3, 1.6%) following. Grade 3 anemia was the most common serious TRAE (grade 3, 39.3%). Only 3 patients (4.9%), however, discontinued treatment because of adverse events (grade 3 anemia, 2 patients; grade 3 vertigo, 1 patient).

Dr Litton concluded, “Talazoparib monotherapy was active in the neoadjuvant setting, with pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens. Treatment-emergent adverse events were consistent with the established safety profile.”

Disclosure: This research was supported by Pfizer Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol. 2021;39:(suppl 15; abstr 505). doi:10.1200/JCO.2021.39.15_suppl.505 

This article originally appeared on Cancer Therapy Advisor