Treatment with abemaciclib as monotherapy induced objective tumor responses and was well-tolerated by patients with HR-positive, HER2-negative metastatic breast cancer, which may allow for prolonged treatment use. These results were detailed in the study, “MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease,” recently presented at the ASCO 2016 meeting in Chicago.
Abemaciclib is a CDK inhibitor selective for CDK4 and CDK6, two molecules (cyclins) involved in cell division. It is an investigational drug for various types of cancer, and was designated a breakthrough therapy by the U.S. Food and Drug Administration in October 2015.
“Abemaciclib is a CDK 4/6 inhibitor,” Adam M. Brufsky, MD, PhD, professor of medicine, associate chief of hematology/oncology, and co-director of the comprehensive breast cancer center at the University of Pittsburgh, said in a news release. “It differs from palbociclib in that it really, predominately, inhibits CDK 4 and not 6.”
MONARCH 1 (NCT02102490) is a Phase 2 single-arm clinical trial evaluating the efficacy and safety of abemaciclib monotherapy in women with HR+/HER2- matastatic breast cancer, whose cancer progressed on or after they were treated with chemotherapy and endocrine therapy. Patients were randomly assigned to receive 200 mg abemaciclib, administered orally, every 12 hours in 28-day cycles until disease progression.
The trial, which opened in June 2014, is expected to finish in April 2017, but final data was collected in April of this year.
Its primary objective is investigator-assessed objective response rate (ORR), evaluated using RECIST v1.1, a response evaluation criteria for solid tumors, with interim and final analyses at 8 and 12 months after the last patient commenced treatment.
Patients in the trial were a median age of 58, and 44.7% had a ECOG score of 1. ECOG is a scale that describes a patient’s level of functioning in terms self-care, daily activity, and physical ability, and level 1 means they are restricted in physically strenuous activity, but are ambulatory and able to carry out light or sedentary work, like office work. Most women (90.2%) had visceral disease, and 85.6% had two or more metastatic sites.
“What was dramatic in this population was that the median PFS [progression free survival] was 5.7 months,” Brufsky said. “More importantly, the confirmed objective response rate was 17.4%. When you look at historical controls in this population, that is about 3 or 4 months longer than we would expect. This is a really interesting finding.”
MONARCH1 results demonstrate that abemaciclib “has potential as a single-agent CDK 4/6 inhibitor in later lines of disease,” Brufsky added.