Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study

Abstract

Background

Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.

Patients and methods

BERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, Cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary endpoint was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association (NYHA) Class III/IV heart failure and of left ventricular ejection fraction (LVEF) declines (≥10 percentage points from baseline and to a value of < 50%). The main efficacy endpoint was pathological complete response (pCR, ypT0/is ypN0). Results are descriptive.

Results

Safety populations were 199 and 198 patients in Cohorts A and B, respectively. Three patients (1.5%; 95% confidence interval [CI]: 0.31–4.34) in Cohort A experienced four NYHA Class III/IV heart failure events. Thirteen patients (6.5%; 95% CI: 3.5–10.9) in Cohort A and four (2.0%; 95% CI: 0.6–5.1) in Cohort B experienced at least one LVEF decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in Cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively).

Conclusion

Treatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab.

Clinical Trial Information

NCT02132949