Long-term cardiac safety and efficacy have been confirmed for the combination of pertuzumab plus trastuzumab in patients with early-stage HER2-positive breast cancer, according to the final analysis of the phase II BERENICE trial reported by Chau T. Dang, MD, and colleagues at the ESMO Breast Cancer Virtual Congress 2021 (Abstract 430).
These data support the use of dual HER2 blockade with pertuzumab/pertuzumab-based regimens, including the combination with dose-dense anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete management of HER2-positive early breast cancer.— Chau T. Dang, MD
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Dr. Dang, of Memorial Sloan Kettering Cancer Center, reported no new cardiac safety issues and a 5-year event-free survival rate of around 90% with neoadjuvant/adjuvant dual HER2-targeting plus anthracycline-containing regimens in patients with early HER2-positive breast cancer.
“These data support the use of dual HER2 blockade with pertuzumab/pertuzumab-based regimens, including the combination with dose-dense anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete management of HER2-positive early breast cancer,” Dr. Dang commented.
About BERENICE
BERENICE was a multicenter, open-label, noncomparative phase II trial designed to establish the cardiac safety of neoadjuvant/adjuvant pertuzumab/trastuzumab with anthracycline-containing chemotherapy in patients with stage IIA to III HER2-positive early breast cancer (< 2 cm, or > 2 mm and node-positive). All patients had a baseline left ventricular ejection fraction of ≥ 55%.
Patients were allocated to receive one of the following regimens:
- Dose-dense doxorubicin plus cyclophosphamide every 2 weeks for 4 cycles followed by weekly paclitaxel for 12 cycles (cohort A)
- Fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for four cycles plus docetaxel every 3 weeks for four cycles (cohort B).
Pertuzumab/trastuzumab was given in both arms, initiated with the taxane and continued after surgery for a total of 17 cycles.
More than 60% of patients in both arms were node-positive (almost half were N1), and more than half had T2 tumors.
Cardiac Safety
As previously reported by Swain et al in Annals of Oncology, the primary trial analysis showed a low incidence of cardiac events during the neoadjuvant period and high rates of total pathologic complete response. Two patients in the dose-dense arm (cohort A) experienced a single class III/IV heart failure event, and one patient experienced two such events. No cardiac events were observed in the FEC arm (cohort B). Declines in left ventricular ejection fraction were observed in 6.5% of patient in cohort A and 2.0% of those in cohort B. Total pathologic complete response rates were approximately 61% in each arm.
Updated 5-Year Outcomes
Dr. Dang reported the 5-year outcomes at end-of-study, including additional safety and efficacy data, after a median follow-up of 64.5 months.
“No new safety concerns arose during long-term follow-up, with a low incidence of cardiac events, drug-related grade ≥ 3 adverse events, and serious adverse events in both cohorts,” she said.
No new safety concerns arose during long-term follow-up, with a low incidence of cardiac events, drug-related grade ≥ 3 adverse events, and serious adverse events in both cohorts.— Chau T. Dang
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No new cardiac safety issues were observed during follow-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 left ventricular ejection fraction episodes occurred during the treatment-free period.
During the treatment interval, 27 (13.6%) patients had at least one left ventricular ejection fraction decrease to ≥ 10% and 12 (6.0%) patients experienced left ventricular ejection fraction < 50% in cohort A, whereas in cohort B, 24 (12.1%) and 7 (3.5%) patients reported these respective left ventricular ejection fraction events.
No episodes of New York Heart Association class III/IV congestive heart failure were observed in cohort A; one (0.5%) episode occurred in cohort B during the treatment-free follow-up period. On treatment, in cohorts A and B, three (1.5%) and two (1.0%) patients, respectively, experienced New York Heart Association class III/IV congestive heart failure. A total of three patients in cohort B did not have available safety data.
As for other safety parameters, for cohort A and cohort B, respectively, grade ≥ 3 adverse events were seen in 1.0% and 2.5% of patients; serious adverse events in 1.5% and 3.5%; non–breast-related second primary malignancies in 0% and 3.0%; and deaths in 3.5% and 6.5%. The most common cause of death in both cohorts was disease progression.
Event-free survival rates at 5 years for cohort A and cohort B, respectively, were 90.8% and 89.2%; as previously reported, at 3 years, they were 93.6% and 90.8%. Overall survival at 5 years was 96.1% and 93.8%, respectively.
The study authors concluded, “The final analysis of BERENICE showed sustained cardiac safety and favorable long-term efficacy outcomes, further supporting neoadjuvant/adjuvant pertuzumab/trastuzumab with standard anthracycline-containing therapies in patients with early-stage HER2-positive breast cancer.”
Disclosure: Dr. Dang disclosed financial relationships with F. Hoffmann-La Roche, Genentech, Daiichi-Sankyo, Lilly, and Puma Biotechnology. For full disclosures of the study authors, visit oncologypro.esmo.org.
