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Neoadjuvant Pertuzumab/Trastuzumab Demonstrates Long-Term Cardiac Safety in HER2-Positive Breast Cancer

No new safety signals occurred with neoadjuvant pertuzumab/trastuzumab at five years
07 May 2021
Anticancer agents & Biologic therapy;  Breast cancer;  Personalised medicine

Patients with stage IIA to III HER2-positive breast cancer demonstrated high rates of event-free survival (EFS) and a low occurrence of cardiac events at 5 years after receiving neoadjuvant/adjuvant pertuzumab plus trastuzumab with standard anthracycline-containing therapies. Chau Dang of the Department of Medicine, Breast Medicine Service, Memorial Sloan Kettering Cancer Centre in New York, USA presented long-term findings from the BERENICE study (NCT02132949) at the ESMO Breast Cancer Virtual Congress 2021, held 5 to 8 May.

Dr. Dang presented data related to the secondary objective, safety and efficacy outcomes at 5-years, which represented the end-of-study analysis with a clinical cut-off date of 25 August 2020.

The multicentre, open-label, non-comparative phase II BERENICE study enrolled patients with stage IIA to III HER2-positive breast cancer and a left ventricular ejection fraction (LVEF) ≥55%. According to physician's choice patients were assigned to be treated with dose-dense doxorubicin/cyclophosphamide every 2 weeks for 4 cycles plus 4 weekly cycles of paclitaxel for 12 cycles (cohort A: n=199) or to receive 5-fluorouracil, epirubicin, cyclophosphamide every 3 weeks for 4 cycles and 4 cycles of docetaxel every 3 weeks (cohort B; n=201). Pertuzumab/trastuzumab every 3 weeks was initiated from the start of taxanes and continued after surgery for a total of 17 cycles.

The primary objective of BERENICE was to illustrate the cardiac safety of neoadjuvant pertuzumab/trastuzumab with anthracycline-containing chemotherapies.

High rates of event-free survival were observed

The 5-year EFS rates were 90.8% (95% confidence interval [CI] 86.5-95.2) in cohort A and 89.2% (95% CI 84.8-93.6) in cohort B, while the 5-year overall survival rates were 96.1% (95% CI 93.3-98.9) and 93.8% (95% CI 90.3-97.2), respectively.

PAM50 classification was available for 339 patients which showed that the majority (51.6%) of patients had HER2-enriched tumours; the 5-year EFS rates in these patients were 93.1% (95% CI 87.2-98.9) in cohort A and 88.3% (95% CI 81.8-94.8) in cohort B.

No new cardiac safety issues were observed during folllow-up. In addition, few events were observed in the treatment-free period and a low incidence of class III/IV congestive heart failure was reported.

The safety analysis comprised 199 cohort A and 198 cohort B patients. Among these patients, no LVEF episodes occurred during the treatment-free period.

During the treatment interval, 27 (13.6%) patients had at least one LVEF decrease to ≥10% and 12 (6.0%) patients experienced LVEF <50% in cohort A, whereas in cohort B 24 (12.1%) and 7 (3.5%) patients reported these respective LVEF events.

No episodes of New York Heart Association class III/IV congestive heart failure were observed in cohort A and one (0.5%) episode occurred in cohort B during the treatment-free follow-up period. On treatment, in cohorts A and B, 3 (1.5%) and 2 (1.0%) patients, respectively, experienced New York Heart Association class III/IV congestive heart failure. A total of 3 patients in cohort B did not have available safety data.

Dr. Evandro de Azambuja of the Jules Bordet Institute in Brussels, Belgium who discussed the study findings commented about favourable long-term efficacy outcomes with pertuzumab/trastuzumab-based (neo)adjuvant regimens. However, the chemotherapy backbone’s contribution cannot be assessed, due to the non-randomised study design. An anthracycline-free regimen was not evaluated in the present study. He said that the low incidence of cardiac events with the pertuzumab/trastuzumab-based regimen given before and after surgery was maintained during the 5-year follow-up. No new safety concerns arose during long-term follow-up, but additional information on cardiac medications/co-morbidities are needed. He also questioned if LVEF assessment by echocardiography is enough to assess cardiac safety.


The investigators noted that the BERENICE study demonstrated favourable long-term efficacy outcomes, and sustained cardiac safety in patients with early HER2-positive breast cancer. They stated that these findings support the use of neoadjuvant/adjuvant pertuzumab plus trastuzumab with standard anthracycline-containing therapies in this patient population.

The study was funded by F. Hoffmann-La Roche.


43O – Dang C, Ewer MS, Delaloge S, et al. Pertuzumab/Trastuzumab in Early Stage HER2-positive Breast Cancer: 5-year and Final Analysis of the BERENICE Trial. ESMO Breast Cancer Virtual Congress 2021 (5-8 May).

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