Results from the EARLY-MYO-BC trial assessing the pyrotinib’s cardiac impacts may help researchers select an appropriate anti-HER2 treatment when managing patients with HER2-positive breast cancer.
Trial Name: Early Detection of Chemotherapy-related Cardiomyopathy in Patients With Breast Cancer Using Cardiac Magnetic Resonance
ClinicalTrials.gov Identifier: NCT04510532
Sponsor: RenJi Hospital
Recruitment Contact: Meng Jiang, MD, +86 13788912766, jiangmeng0919@163.com
Completion Date: September 2023
The EARLY-MYO-BC (NCT04510532) study aims to assess the cardiac impacts of pyrotinib for patients with HER2-positive breast cancer patients and determine whether pyrotinib combined with trastuzumab (Herceptin) is a reasonable dual HER2 blockade regimen with regard to cardiac safety.1
Pyrotinib is a tyrosine kinase inhibitor targeting HER2 that has been used to treat patients with breast cancer. Pyrotinib plus capecitabine demonstrated survival improvement vs lapatinib (Tykerb) in the
Research from multiple studies of pyrotinib show that at a median follow-up of 84.2 months (95% CI, 74.7-93.7 months), the estimated median progression-free survival (PFS) for a cohort of 66 patients was 9.2 months (95% CI, 5.4-12.9 months) and the median overall survival (OS) was 31.0 months (95% CI: 16.5–45.5 months). For patient who received pyrotinib monotherapy, the PFS and OS were 8.2 months and 27.1 months vs 22.1 months and 37.4 months in the pyrotinib plus capecitabine cohort of patients.2
According to a biomarker analysis from the study, patients with concomitant mutations from multiple pathways in HER2-related signaling had significantly worse PFS (7.3 v 26.1 months; P = .003) and OS (25.1 v 48.0 months, P = .013) rates compared with patients who had none or 1 genetic alteration.
However, the agent has also resulted in less well-understood cardiotoxicity. The cardiotoxicity, which has become the most common cause of non-cancer death among this patient population, from this agent has been rarely studied in single or dual HER2 blockade regimens.1
In the prospective, open-label, observational EARLY-MYO-BC study, investigators will further assess the cardiac impacts of pyrotinib. Patients with HER2-positive breast cancer will be enrolled and receive 4 cycles of neoadjuvant therapy with pyrotinib or pertuzumab (Perjeta) added to trastuzumab prior to radical breast cancer surgery.2
Those included in the trial will undergo comprehensive cardiac assessment before and after neoadjuvant therapy. At baseline, demographic features will be collected from patients, including age, body mass index, blood pressure, heart rate, risk factors for cardiovascular events, tumor location, tumor stage, and history of cancer and other diseases.1 Then, laboratory measurements utilized for cardiac assessment are cardiac, complete blood counts, hepatic function markers, renal function markers, fasting glucose, and inflammatory markers. For the cardiac examination of patients, electrocardiogram, echocardiography, cardiopulmonary exercise, and cardiovascular magnetic resonance data will be recorded in the study database.
The first group will be treated with pyrotinib 400 mg orally once a day with cisplatin 25 mg/m2 at day 1, 8, 15, paclitaxel 80 mg/m2 at day 1, 8, 15, 22, and trastuzumab at 4 mg/kg at loading dose, then 2 mg/kg per week which will be administered intravenously (IV). The pertuzumab group treatment regimen then consists of the same regimen of cisplatin, paclitaxel, and trastuzumab as in the pyrotinib group, with the addition of IV pertuzumab at an 840 mg loading dose, followed by 420 mg every 3 weeks in the ambulatory chemotherapy ward.
Approximately 300 patients will be included in the study. Enrollment in the trial is open to female patients between 18 and 70 years of age with newly diagnosed and histologically confirmed early or locally advanced HER2-positive invasive breast cancer. Patients must have no signs of cardiac discomfort, have a normal range of baseline cardiac biomarkers, have not received any prior systemic anti-cancer therapy for advanced disease, and have an ECOG performance status of 0-1.3
One month after the first measurement, one-fourth of the patients will be randomly chosen for imaging measurement reproducibility assessment. Interobserver and intraobserver imaging measurement reproducibility will be assessed by intraclass correlation analyses.1
Investigators are assessing the primary end point of relative change in global longitudinal strain from baseline to completion of neoadjuvant therapy by echocardiography and the secondary end points of myocardial diffuse fibrosis, myocardial edema, cardiac volumetric assessment by CMR, diastolic function by echocardiography, and exercise capacity by CPET.
The EARLY-MYO-BC trial is the first to explore the cardiac impacts of pyrotinib in the neoadjuvant setting for this patient population. Patients are currently being recruited for the trial, and the study has an estimated completion date of September 2023.
