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Abemaciclib/Fulvestrant/Trastuzumab for Patients With Previously Treated HR-Positive, HER2-Positive Advanced Breast Cancer


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In the phase II monarcHER trial reported in The Lancet Oncology, Sara M. Tolaney, MD, 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.

Sara M. Tolaney, MD

Sara M. Tolaney, MD

Study Details

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.

Progression-Free Survival

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 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.”
— Sara M. Tolaney, MD, and colleagues

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Adverse Events

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.”

Dr. Tolaney, of Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Eli Lilly and Company. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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