The combination of abemaciclib, fulvestrant, and trastuzumab showed significant improvement in progression-free survival (PFS) versus standard-of-care chemotherapy plus trastuzumab while showing a tolerable safety profile in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, according to a study published by The Lancet Oncology.

There are few effective treatment options for patients with HER2-positive breast cancer who have received 2 or more previous therapies for advanced disease, according to the study authors. The monarcHER trial aimed to compare the efficacy of abemaciclib plus trastuzumab with or without fulvestrant versus physician's choice of standard-of-care chemotherapy plus trastuzumab in women with advanced breast cancer. 

The trial was completed across 75 hospitals, clinics, and medical centers in 14 countries, with eligible patients being women aged 18 years and older who had hormone receptor (HR)-positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease. The patients also had to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and had previously received at least 2 HER2-targeted therapies for advanced disease, according to the study authors. 

Patients were randomly assigned 1:1:1 to the abemaciclib, trastuzumab, and fulvestrant (group A), abemaciclib and trastuzumab (group B), or standard-of-care chemotherapy and trastuzumab (group C). Oral abemaciclib, 150 mg 12 hourly, was administered on days 1-21 of a 21 day cycle, intravenous trastuzumab 8 mg/kg on cycle 1 day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle, and intramuscular fulvestrant 500 mg on days 1, 15, and 29, and once every 4 weeks thereafter. Standard-of-care chemotherapy was administered as specified by the product label.

The primary endpoint was investigator-assessed PFS in the intention-to-treat population, first testing group A versus group C, and then group B versus group C if the results from the first testing group were significant. In addition, safety was assessed in all patients who had received at least 1 dose of study treatment, according to the study authors.

Three hundred and twenty-five patients were screened between May 31, 2016, and February 28, 2018, of whom 237 eligible patients were enrolled and randomly assigned to groups A, B, and C. Median follow-up was 19 months, and the study met its primary endpoint. No difference was observed between median PFS in groups B and C.

The most common grade 3-4 treatment-emergent adverse events (AEs) in groups A, B, and C was neutropenia. In group A, the most common serious AEs included pyrexia, diarrhea, urinary tract infection, and acute kidney injury. Group B’s AEs included diarrhea and pneumonitis, whereas group C’s were neutropenia and pleural effusion. The treatment attributed 2 deaths, with 1 being related to pulmonary fibrosis in group B and 1 due to febrile neutropenia in group C.

The results suggest that a chemotherapy-free regimen may potentially be an alternative treatment option for patients with HR-positive, HER2-positive advanced breast cancer, according to the study authors.


REFERENCE

Tolaney SM, Wardley AM, Zambelli S, et al. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. The Lancet Oncology. Published April 27, 2020. Doi: https://doi.org/10.1016/S1470-2045(20)30112-1.