An interim analysis from the Phase 3 trial known as MONARCH 3 showed that adding abemaciclib to an aromatase inhibitor — Femara (letrozole) or Arimidex (anastrozole) — helped to treat certain postmenopausal women with advanced breast cancer, lengthening their time to disease progression.
The trial studied the combination, versus an aromatase inhibitor alone, in women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. With these findings MONARCH 3 met its primary endpoint, in addition to a secondary endpoint, that of objective response rate (ORR).
“Today marks another important milestone in our clinical development program for abemaciclib, a drug we believe has the potential to be best in class,” Levi Garraway, senior vice president, global development and medical affairs, Lilly Oncology, said in a news release. “We are very excited about the results seen in patients with breast cancer … Along with additional abemaciclib clinical trials in other tumor types, these data underscore Lilly’s commitment to delivering life-changing medicines to treat and cure people living with cancer around the world.”
When cell’s divide, several “checkpoint” proteins control the division process. When these proteins are faulty, uncontrolled cell growth may result, leading to cancer formation.
In many cancers, increased signaling from the checkpoint proteins CDK4 and CDK6 has been shown to heighten cell proliferation in an uncontrolled manner, which blocking (or inhibiting) these proteins could prevent. Abemaciclib is a CDK4/6 oral inhibitor. In HR-positive breast cancer cell lines, abemaciclib was able to halt cell proliferation.
Abemaciclib is currently being evaluated in combination with an aromatase inhibitor in postmenopausal women with HR-positive, HER-negative advanced breast cancer. The MONARCH 3 trial (NCT02107703) is a global, double-blind, placebo-controlled study evaluating the combination versus aromatase inhibitor alone as an initial endocrine-based therapy for patients who have not received prior systemic therapy for advanced disease.
A total of 493 women were randomized in a 2:1 ratio to receive abemaciclib (150 mg) or placebo orally, twice a day, in combination with either Femara (2.5 mg) or Arimidex (1 mg) until disease progression or unacceptable toxicity.
The study’s primary endpoint is progression-free survival, and secondary endpoints include ORR, overall survival, and safety.
In addition to meeting its primary objective and ORR secondary, abemaciclib’s safety profile was seen to be similar to other studies of this treatment. The most common adverse events were diarrhea, fatigue, nausea, and low levels of a type of white blood cell called neutrophils.
The company will present data from this trial at a medical conference later this year.