BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer

Abstract

BERENICE (NCT02132949) assessed the cardiac safety of the neoadjuvant–adjuvant pertuzumab–trastuzumab-based therapy for high-risk, HER2-positive early breast cancer (EBC). We describe key secondary objectives at final analysis. Eligible patients received dose-dense doxorubicin and cyclophosphamide q2w × 4 ➝ paclitaxel qw × 12 (Cohort A) or 5-fluorouracil, epirubicin, cyclophosphamide q3w × 4 ➝ docetaxel q3w × 4 (B) as per physician’s choice. Pertuzumab–trastuzumab (q3w) was initiated from the taxane start and continued post-surgery to complete 1 year. Median follow-up: 64.5 months. There were no new cardiac issues and a low incidence of Class III/IV heart failure (Cohort B only: one patient (0.5%) in the adjuvant and treatment-free follow-up (TFFU) periods). Fourteen patients (7.7%) had LVEF declines of ≥10% points from baseline to <50% in Cohort A, as did 20 (10.5%) in B during the adjuvant period (12 (6.2%) in A and 7 (3.6%) in B during TFFU). The five-year event-free survival rates in Cohorts A and B were 90.8% (95% CI: 86.5, 95.2) and 89.2% (84.8, 93.6), respectively. The five-year overall survival rates were 96.1% (95% CI: 93.3, 98.9) and 93.8% (90.3, 97.2), respectively. The final analysis of BERENICE further supports pertuzumab–trastuzumab-based therapies as standard of care for high-risk, HER2-positive EBC.

Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

“…A comprehensive pooled safety analysis is challenging because safety data were not collected and reported in the same way in all studies. Safety data from the individual studies has been extensively reported, and suggest that toxicity is not markedly increased with the addition of pertuzumab except for diarrhea which is higher particularly in the neoadjuvant setting where it is given concurrently with chemotherapy ( Table S3 ; [ 5 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 24 ]). Docetaxel plus pertuzumab and trastuzumab was compared with docetaxel plus trastuzumab for treatment of HER2-positive EBC in the NEOSPHERE trial [ 14 , 17 ].…”

“…Thirteen of the 199 patients (6.5%) in Cohort A and four of the 198 (2.0%) patients in Cohort B had symptomatic and asymptomatic LVEF declines to <50% and by ≥10 percentage points from baseline. The 5-year follow-up data showed a similarly low incidence of cardiac toxicity [ 24 ]. These data suggest an acceptable cardiac toxicity profile with the addition of pertuzumab to trastuzumab and these chemotherapy regimens, and thus support the safety of continuation of pertuzumab plus trastuzumab from the neoadjuvant to adjuvant setting.…”

“…We pooled patient-level data from five randomized neoadjuvant trials in patients with HER2-positive EBC (including those with inflammatory breast cancer) who received trastuzumab, pertuzumab, or both as part of a systemic neoadjuvant regimen and for whom individual patient-level data were available. The following studies were included: HannaH (NCT00950300) [ 15 , 21 ], NeoSphere (NCT00545688) [ 14 , 17 ], TRYPHAENA (NCT00976989) [ 5 , 16 ], BERENICE (NCT02132949) [ 19 , 24 ], and KRISTINE (NCT02131064) [ 18 , 20 ]. All studies were conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.…”

Targeting Breast Cancer: An Overlook on Current Strategies

“…It is approved by FDA for use in association with trastuzumab and docetaxel in MBC, and in combination with trastuzumab and chemotherapy as neoadjuvant or adjuvant therapy in non-metastatic disease. The combination of pertuzumab and trastuzumab has shown low cardiac toxicity and favorable efficacy outcomes as demonstrated by the BERENICE study [ 224 ].…”

Review of the status of neoadjuvant therapy in HER2-positive breast cancer

“…Cardiac safety was the primary endpoint: left ventricular systolic dysfunction (LVSD) incidence was low (5.6%) in the neoadjuvant setting in the anthracycline-containing arm ( 29 ). Furthermore, the BERENICE trial demonstrated cardiac safety in both dose-dense and standard anthracycline-containing regimens in combination with trastuzumab and pertuzumab ( 30 , 31 ).…”