Talazoparib Is Active in gBRCA1/2 Mutation-Positive, HER2-Negative Early Breast Cancer

In Clinical Studies News by Barbara Jacoby

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By: Walter Alexander

From: cancertherapyadvisor.com

Neoadjuvant talazoparib demonstrated activity and pathologic complete response (pCR) rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens in a phase 2 trial of patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, HER2-negative early breast cancer.

The results were presented by Jennifer Keating Litton, MD, of The University of Texas MD Anderson Cancer Center in Houston, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Dr Litton noted that talazoparib is a PARP inhibitor 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 gBRCA1/2 mutations 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. Secondary endpoints included pCR by investigator assessment (INV) and residual cancer burden (RCB) by ICR (with 0=pCR, I=minimal, II=moderate, III=extensive).

The evaluable population (48 patients) included those who received at least 80% of the talazoparib dose prescribed at treatment start who underwent breast surgery and pCR assessment, as well as those who progressed before pCR. The intention-to-treat (ITT) population (61 patients) included all patients who received at least 1 dose of talazoparib.

The mean patient age was 44.6 years. All patients had triple-negative breast cancer, 60 with adenocarcinoma and 1 with squamous cell histology. Twenty patients had stage I disease, 27 patients had stage II, and 14 patients had stage III.

The 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). Ten patients (16.4%) discontinued treatment due to progressive disease, 1 patient experienced treatment disruption due to COVID-19 restrictions, and 2 disrupted treatment for other reasons.

In the evaluable population, the pCR rate was 45.8% by ICR and by INV. The RCB 0 rate was 45.8%, the RCB I rate was 0%, the RCB II rate was 31.3%, and the RCB III rate was 0%.

The pCR rates in the ITT population were 49.2% by ICR and 47.5% by INV. The RCB rates were 30% for RCB 0, 1.6% for RBC I, 27.9% for RCB II, and 0% for RCB III.

Treatment-related adverse events (TRAEs) were reported in 98.4% of patients overall. The most common were fatigue (77.0%), nausea (63.9%), and alopecia (57.4%). Grade 3 anemia was the most common serious TRAE (39.3%).

Three patients (4.9%) discontinued treatment because of TRAEs (grade 3 anemia, 2 patients; grade 3 vertigo, 1 patient).

“Talazoparib monotherapy was active in the neoadjuvant setting, with pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens,” Dr Litton concluded. “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.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.

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