Sara M. Tolaney, MD
In the phase II monarcHER trial reported in The Lancet Oncology, Sara M. Tolaney, MD, of Dana-Farber Cancer Institute, Boston, and colleagues, found that the combination of abemaciclib, fulvestrant, and trastuzumab prolonged progression-free survival vs trastuzumab plus standard-of-care chemotherapy in patients with previously treated advanced hormone receptor (HR)-positive, HER2-positive breast cancer.1
The open-label trial included 237 patients from sites in 14 countries with unresectable locally advanced, recurrent, or metastatic disease who had previously received at least two HER2-targeted therapies. Patients were randomly assigned 1:1:1 between May 2016 and February 2018 to receive abemaciclib/fulvestrant/trastuzumab (n = 79), abemaciclib/trastuzumab (n = 79), or trastuzumab plus physician’s choice of standard-of-care single-agent chemotherapy (n = 79).
Abemaciclib was given at 150 mg twice daily on days 1 to 21 of 21-day cycles; trastuzumab was given at 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 was given at 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. The most common chemotherapy agents given in the trastuzumab/chemotherapy group were vinorelbine (38%), capecitabine (26%), eribulin (17%), and gemcitabine (11%). Treatment was given until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival. Significance of progression-free survival was defined as a two-sided P < .2.
Median follow-up was 19.0 months. Median progression-free survival was 8.3 months (95% confidence interval [CI] = 5.9–12.6 months) in the abemaciclib/fulvestrant/trastuzumab group vs 5.7 months (95% CI = 5.4–7.0 months) in the trastuzumab/chemotherapy group (hazard ratio [HR] = 0.67, P = .051). Median progression-free survival in the abemaciclib/trastuzumab group was 5.7 months (95% CI = 4.2–7.2 months), which did not significantly differ from that in the trastuzumab/chemotherapy group (HR = 0.94, P = .77).
At the time of the progression-free survival analysis, overall survival data were immature; death had occurred in 39% of patients in the abemaciclib/fulvestrant/trastuzumab group, 38% of those in the abemaciclib/trastuzumab group, and 41% of those in the trastuzumab/chemotherapy group. Overall response rates were 33% (P = .004 vs trastuzumab plus chemotherapy), 14%, and 14% in the three groups, respectively.
The most common grade 3 or 4 adverse event across all groups was neutropenia, occurring in 27%, 22%, and 26% of patients, respectively. The most common serious adverse events were pyrexia (4%), diarrhea (3%), urinary tract infection (3%), and acute kidney injury (3%) in the abemaciclib/fulvestrant/trastuzumab group; diarrhea (3%) and pneumonitis (3%) in the abemaciclib/trastuzumab group; and neutropenia (6%) and pleural effusion (3%) in the trastuzumab/chemotherapy group. Two deaths were considered related to treatment: one due to pulmonary fibrosis in a patient in the abemaciclib/trastuzumab group and one due to febrile neutropenia in the trastuzumab/chemotherapy group.
The investigators concluded: “The combination of abemaciclib, fulvestrant, and trastuzumab significantly improved progression-free survival vs standard-of-care chemotherapy plus trastuzumab, while showing a tolerable safety profile. Our results suggest that a chemotherapy-free regimen might potentially be an alternative treatment option for patients with hormone receptor–positive, HER2-positive advanced breast cancer.”
Disclosure: The study was funded by Eli Lilly and Company. For full disclosures of the study authors, visit thelancet.com.
1. 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. Lancet Oncol 21:763-775, 2020.