In 2017 the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor, Abemaciclib (tentatively known as bomacitinib), for marketing, giving new hope for the treatment of advanced breast cancer.
Abemaciclib is primarily used in hormone receptor-positive, HER2-negative advanced metastatic breast cancer, either alone or in combination with endocrine agents such as fulvestrant or aromatase inhibitors.
How do CDK4/6 inhibitors work against cancer?
In human cells, there is a protein called cell cycle protein-dependent kinase (CDK for short), which is a key factor in regulating cell division and promoting cell proliferation and growth. This role is of course no exception for cancer cells.
CDK4/6 are two major members of the cell cycle protein-dependent kinase family, and the corresponding CDK4/6 inhibitors precisely block the cell cycle, forcing tumor cells to stop proliferating. As a member of the CDK4/6 inhibitor class of drugs, Abemaciclib controls breast cancer progression in exactly this way.
Abemaciclib single agent benefits about 40% of patients
In the phase II clinical trial MONARCH 1 Abemaciclib demonstrated some control of tumor progression, but some adverse effects specific to CDK4/6 inhibitors also occurred.
Selected for study were 132 hormone receptor-positive, HER2 -negative patients with metastatic breast cancer who had undergone 1 to 2 prior chemotherapy and outgrown tumor progression during endocrine therapy.
Patients given Abemaciclib treatment had an objective remission rate of approximately 20%, with 42.4% of patients having a treatment benefit, a median progression-free survival of 6.0 months, and a median overall survival of up to 17.7 months .
Diarrhea is Abemaciclib the most common adverse reaction, with an incidence of 90.2 %. Although the incidence is high, it is not severe, with only 1 person discontinuing the drug during treatment due to severe diarrhea. Neutropenia is another common adverse effect, and other side effects include fatigue, nausea, and loss of appetite.
Abemaciclib combined with fulvestrant multiplies remission rates
The MONARCH 2 study provides a reference for Abemaciclib combined with fulvestrant therapy. This phase III clinical trial involved 669 patients with advanced breast cancer, all of whom had failed out of endocrine therapy. Compared with everolimus therapy alone, after Abemaciclib combined with fulvestrant, patients had a 7.1 month longer progression-free survival (16.4 months vs. 9.3 months), a 45% lower risk of progressive tumor progression, and more than double the objective remission rate to nearly 50%.
Likewise, adverse reactions with Abemaciclib were mostly diarrhea (87.3%), neutropenia (59.2%), and leukopenia (43.7%).
Continuing to explore: more people, more combinations
The exploration of Abemaciclib for breast cancer continues in several major directions:
- More breast cancer types. In addition to hormone receptor-positive/HER2 -negative breast cancers, researchers are focusing on advanced triple-negative breast cancers, as well as hormone receptor-positive and HER2 -positive breast cancers.
- More combination therapy. In addition to combining with endocrine agents, the powerful combination of Abemaciclib with immunotherapy is being studied.
- Chinese patients. Chinese breast cancer patients are also a focus of research and are still predominantly hormone receptor-positive/HER2 negative breast cancer. In addition, treatment attempts for high-risk early-stage breast cancer are underway.
Summary
For advanced breast cancer that is hormone receptor positive and HER2 negative, Abemaciclib alone or in combination may be considered when choosing a treatment option:
- After failure of endocrine therapy, Abemaciclib single-agent objective remission rates approach 20%;
- After failure of endocrine therapy, fulvestrant + Abemaciclib, substantially improved disease control and prolonged progression-free survival in patients.
The CDK4/6 inhibitor Abemaciclib has achieved better outcomes in advanced breast cancer, but the adverse effects it brings, such as diarrhea and neutropenia, need attention. Expect Abemaciclib to have new breakthroughs in Chinese breast cancer patients.