Lowell L. Hart, MD
Abemaciclib (Verzenio) has emerged as a promising agent for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, according to Lowell L. Hart, MD.
The CDK4/6 inhibitor was approved by the FDA for the frontline treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in February 2018. This followed the September 2017 approval of the agent for use in combination with fulvestrant (Faslodex) in women with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy.
In a presentation during the 17th Annual International Congress on the Future of Breast Cancer®
East, Hart, scientific director of Clinical Research at Florida Cancer Specialists, discussed the recent data with abemaciclib in patients with HR-positive, HER2-negative metastatic breast cancer.1
The phase III randomized, double-blind MONARCH 2 trial combined abemaciclib plus fulvestrant in women who recurred or progressed on or after endocrine therapy.
The 16-month progression-free survival (PFS) of patients who received abemaciclib plus fulvestrant was 16.4 months (95% CI, 14.4-19.3) compared with 9.3 months (95% CI, 7.4-12.7) for placebo plus fulvestrant (HR, 0.553; 95% CI, 0.449-0.681; P
Patients with clinical characteristics such as primary resistance and visceral disease had a less favorable prognosis, and often progressed within 2 years on therapy, Hart added.
"PFS results in subgroups, including those with concerning clinical characteristics, were consistent with the intent-to-treat (ITT) population," Hart explained. "Preplanned subgroup analyses of PFS were performed for stratification factors of disease site, endocrine resistance, and other potential prognostic factors that included measurable diseases at baseline, number of organs involved, age, region, race, progesterone receptor status, and an ECOG [performance] score."
Median PFS in patients with primary resistance was 15.3 months (95% CI, 12.4-24.1) with abemaciclib plus fulvestrant compared with 7.9 months (95% CI, 5.7-11.4) with placebo plus fulvestrant (HR, 0.454; 95% CI, 0.306-0.674).3
For those with visceral disease, the median PFS was 14.7 months (95% CI, 13.0-17.4) with abemaciclib plus fulvestrant compared with 6.5 months (95% CI, 5.6-8.7) with placebo plus fulvestrant (HR, 0.481; 95% CI, 0.369-0.627).
At the time of the primary PFS analysis, the overall survival (OS) data were not mature but 20 patients had died, reported Hart. The overall response rate (ORR) was 48.1% (95% CI, 42.6-53.6) in patients who received abemaciclib plus fulvestrant and progressed on or after endocrine therapy. Of those 153 patients, 3.5% achieved a complete response (CR) and 44.7% achieved a partial response (PR). For patients who received placebo plus fulvestrant, the ORR was 21.3% (95% CI, 15.1-27.6) and all responses (n = 35) were PRs.
The median duration of response (DoR) was a secondary endpoint of the trial. The combination of abemaciclib and fulvestrant had a median DoR of 22.8 months (95% CI, 15.8-26.4) compared with 13.9 months (95% CI, 11.2-25.6) for placebo plus fulvestrant.
The MONARCH 2 results led to the September 2018 FDA approval of the agent in combination with fulvestrant in women with HR-positive, HER2-negative advanced disease with progression following endocrine therapy.
Another use for CDK4/6 inhibitors is in the frontline setting along with an aromatase inhibitor (AI), Hart said.
"In general, most of the gurus in the field that I have talked to feel that an AI and a CDK4/6 inhibitor should be your default," said Hart. "As a default, it is hard to argue with the data."
MONARCH 3 was a phase III, randomized, double-blind, placebo-controlled trial that evaluated abemaciclib plus an AI as initial endocrine-based therapy. This study included patients with HR-positive, HER2-negative locoregionally recurrent or metastatic breast cancer. The primary endpoint of this trial was PFS, with secondary endpoints of OS, ORR, and DoR.
The combination of abemaciclib and an AI showed a median PFS of 28.2 months (95% CI, 23.5-not reached [NR]) compared with 14.8 months (95% CI, 11.2-19.2) for placebo plus an AI, (HR, 0.54; 95% CI, 0.418-0.698; P
In a preplanned subgroup analysis, patients with concerning clinical characteristics were evaluated. The PFS in patients with liver metastases treated with abemaciclib plus an AI was 15.0 months (95% CI, 7.4-23.7) versus 7.2 months (95% CI, 2.1-14.0) for placebo plus an AI, (HR, 0.477; 95% CI, 0.272-0.837).