Abemaciclib Granted Breakthrough Therapy Designation for Advanced Breast Cancer

Of all breast cancer diagnoses in the United States, approximately 20% to 30% will become metastatic.¹ Because of this, it is crucial to develop new therapies. Fortunately, a new treatment option may become available soon.

Abemaciclib (LY2835219), a cyclin-dependent kinase (CDK) 4 and 6 inhibitor for patients with refractory hormone receptor-positive or metastatic breast cancer, has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA).²

Breakthrough Therapy Designation expedites the development and review of drugs that treat serious conditions, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.

In this scenario, this designation is based on data from the breast cancer cohort expansion of a phase I trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. These data were first presented at the San Antonio Breast Cancer Symposium in 2014.

Combinations of abemaciclib with endocrine therapies demonstrated manageable safety and early clinical evidence of antitumor activity in a phase Ib study announced at this year's 2015 American Society of Clinical Oncology (ASCO) annual meeting.³ This study (NCT02057133) evaluated safety, pharmacokinetics, and antitumor activity of abemaciclib combined with endocrine or HER2-targeted therapies for metastatic breast cancer.⁴

A total of 65 patients were prescribed abemaciclib (200 mg every 12 hours) by December 16, 2014, in Parts A-D: Letrozole 2.5 mg daily (Part A), anastrozole 1 mg daily (Part B), tamoxifen 20 mg daily (Part C), exemestane 25 mg daily (Part D). Participants had a median age of 57 years (age range: 28-77), and a median of three prior systemic therapies (treatment range: 1-8) for breast cancer. The disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) was 67% for Parts A and B (letrozole and anastrazole [36 patients]) with two confirmed PRs, and 75% for Part C (tamoxifen [16 patients]).

The most common (≥ 20% overall in Parts A-D) side effects were diarrhea, fatigue, nausea, neutropenia, abdominal pain, decreased appetite, vomiting, and anemia.

The maker of abemaciclib, Eli Lilly, have moved into phase II  with their MONARCH 1 trial evaluating the use of abemaciclib as monotherapy in women with hormone receptor-positive, HER2-negative, metastatic breast cancer. In addition, Lilly is evaluating abemaciclib in two phase III clinical trials: MONARCH 2 to evaluate the combination of abemaciclib and fulvestrant in postmenopausal patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer, and MONARCH 3 to evaluate the combination of abemaciclib and a nonsteroidal aromatase inhibitor in patients with hormone receptor-positive , HER2-negative, locoregionally recurrent or metastatic breast cancer.

References:

• Metastatic Breast Cancer Network. (2015). 13 Facts Everyone Should Know About Metastatic Breast Cancer.
• Eli Lilly and Company. (2015).Lilly Receives FDA Breakthrough Therapy Designation for Abemaciclib - a CDK 4 and 6 Inhibitor - in Advanced Breast Cancer.
• Tolaney SM, Beeram M, Beck JT, et al. (2015). A phase Ib study of abemaciclib with therapies for metastatic breast cancer. ASCO University.
• National Institutes of Health. (2015).  A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread. ClinicalTrials.gov.