medwireNews: The BERENICE investigators report a low incidence of cardiac events with the use of pertuzumab–trastuzumab-based neoadjuvant and adjuvant regimens in patients with HER2-positive, early breast cancer after 5 years of follow-up.
Speaking at the ESMO Breast Cancer Virtual Congress 2021, presenting author Chau Dang (Memorial Sloan Kettering Cancer Centre, New York, USA) noted that the low rates of heart failure and significant left ventricular ejection fraction (LVEF) declines observed in the primary analysis were maintained over longer follow-up.
The 397 patients with stage IIA–III disease recruited to the open-label, phase 2 cardiac safety study were assigned by physician’s choice to receive one of the neoadjuvant treatment regimens outlined below:
- four cycles of dose-dense doxorubicin plus cyclophosphamide (AC) followed by 12 cycles of weekly paclitaxel alongside four cycles of concurrent pertuzumab–trastuzumab every 3 weeks;
- four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks followed by four cycles of docetaxel alongside four cycles of concurrent pertuzumab–trastuzumab every 3 weeks.
Patients in both cohorts then received 13 cycles of adjuvant pertuzumab–trastuzumab on the same schedule.
At a median follow-up of 64.5 months, three patients in the dose-dense AC group and two in the FEC group experienced congestive heart failure of class III or IV as per the New York Heart Association classification. There were no and one case, respectively, during the treatment-free follow-up.
Clinically significant LVEF decline – defined as a decrease of at least 10% from baseline to a value below 50% – occurred in 13.6% of patients in the dose-dense AC cohort and 12.1% of those in the FEC cohort, with a respective 6.0% and 3.5% of cases occurring in the treatment-free follow-up period.
“No new safety concerns arose during long-term follow-up,” said Dang, and the incidence of grade 3 or worse adverse events (AEs) and serious AEs in the dose-dense AC and FEC cohorts was low during the treatment-free follow-up period, at 1.0% versus 2.5% and 1.5% versus 3.5%, respectively.
The long-term efficacy outcomes with the dual HER2 blockade-based regimens were “favorable,” she added, with 5-year event-free survival rates of 90.8% and 89.2% in the dose-dense AC and FEC groups, respectively, and corresponding 5-year overall survival rates of 96.1% and 93.8%.
“These data support the use of dual HER2-blockade with pertuzumab–trastuzumab-based regimens, including in combination with dose-dense, anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete management of HER2-positive [early breast cancer],” concluded the presenting author.
Discussant Evandro de Azambuja, from Institut Jules Bordet in Brussels, Belgium, also described the cardiac safety and efficacy data as “favorable,” but highlighted the lack of baseline information on cardiac medications and comorbidities.
He also questioned whether “LVEF assessment by echocardiography [is] enough to assess cardiac safety,” as LVEF decline is a late effect of cardiotoxicity, and recommended the evaluation of global longitudinal strain to identify early subclinical LV dysfunction and the use of cardiac biomarkers in future trials.
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