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 end point was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association class III/IV heart failure and of left ventricular ejection fraction declines (≥10 percentage-points from baseline and to a value of <50%). The main efficacy end point was pathologic 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% to 4.34%] in cohort A experienced four New York Heart Association class III/IV heart failure events. Thirteen patients (6.5%; 95% CI 3.5% to 10.9%) in cohort A and four (2.0%; 95% CI 0.6% to 5.1%) in cohort B experienced at least one left ventricular ejection fraction 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.

中文翻译：

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帕妥珠单抗，曲妥珠单抗以及基于蒽环类和紫杉烷类的标准化疗用于HER2阳性局限性乳腺癌（BERENICE）患者的新辅助治疗：II期，开放标签，多中心，多国心脏安全性研究。

背景抗HER2治疗与增加心脏毒性的风险有关，尤其是在含有蒽环类药物的治疗方案中。我们报告了帕妥珠单抗，曲妥珠单抗和化疗在HER2阳性早期乳腺癌的新辅助治疗中的心脏安全性。患者和方法BERENICE（NCT02132949）是一项对心脏功能正常的患者进行的非随机，II期，开放标签，多中心，多国研究。在新辅助期，队列A患者接受了四个剂量密集的阿霉素和环磷酰胺治疗，然后接受12个剂量的标准紫杉醇联合四个标准的曲妥珠单抗和帕妥珠单抗治疗。队列B患者接受了四个标准的氟尿嘧啶/厄普霉素/环磷酰胺周期，然后是四个多西他赛周期以及四个标准的曲妥珠单抗和帕妥珠单抗周期。主要终点是新辅助治疗期间的心脏安全性，通过纽约心脏协会III / IV级心力衰竭的发生率和左心室射血分数的降低（相对于基线≥10个百分点，并低于50％）进行评估。主要功效终点是病理完全缓解（pCR，ypT0 /是ypN0）。结果是描述性的。结果A组和B组的安全人群分别为199和198名患者。3名患者[1.5％；A组的95％置信区间（CI）为0.31％至4.34％]经历了四次纽约心脏协会的III / IV级心力衰竭事件。队列A中的13名患者（6.5％; 95％CI 3.5％至10.9％）和队列B中的四名患者（2.0％; 95％CI 0.6％至5.1％）至少有一个左心室射血分数下降。没有发现新的安全信号。pCR率为61。A组和B组分别为8％和60.7％。pCR率最高的是富含HER2的PAM50亚型（分别为75.0％和73.7％）。结论帕妥珠单抗，曲妥珠单抗和常见的含蒽环类药物的方案用于早期乳腺癌的新辅助治疗可产生心脏和一般安全性以及pCR率，与先前使用帕妥珠单抗的研究一致。临床试验信息NCT02132949。