Abemaciclib - A Breakthrough for Advanced Breast Cancer
Abemaciclib - A Breakthrough for Advanced Breast Cancer
Breast cancer is the most common cancer among women worldwide, and about 70% of cases are hormone receptor (HR)-positive, meaning that they depend on hormones such as estrogen and progesterone for growth. However, some of these cancers also have mutations in a gene called HER2, which encodes a protein that stimulates cell growth and survival. These mutations make the cancer cells more resistant to hormone therapy and more aggressive.
For many years, the standard treatment for HR-positive, HER2-negative advanced breast cancer has been hormone therapy, either alone or in combination with other drugs that interfere with cell cycle progression, such as CDK4/6 inhibitors. CDK4/6 inhibitors are a class of drugs that block the activity of two proteins, CDK4 and CDK6, that are involved in regulating cell division. By doing so, they prevent the cancer cells from growing and dividing uncontrollably.
However, not all patients respond to CDK4/6 inhibitors, and some develop resistance over time. Therefore, there is a need for new and effective treatments for this type of breast cancer.
One such treatment is abemaciclib, a novel CDK4/6 inhibitor that has some unique features compared to other drugs in its class. Abemaciclib is the drug’s non-branded name. Its brand name is Verzenios12. Abemaciclib works by blocking CDK4 and CDK6 more selectively and continuously than other CDK4/6 inhibitors, which may result in more potent and durable effects on the cancer cells.
Abemaciclib has been tested in several clinical trials involving patients with HR-positive, HER2-negative advanced breast cancer who have received previous treatment with hormone therapy and/or other drugs. The results of these trials have been impressive.
In the MONARCH 2 trial, abemaciclib plus fulvestrant (a type of hormone therapy) significantly improved progression-free survival (the time without disease worsening) and overall survival (the time from randomization to death from any cause) compared to placebo plus fulvestrant in patients who had progressed on or after endocrine therapy. The median progression-free survival was 16.4 months in the abemaciclib group versus 9.3 months in the placebo group, which translates to a 45% reduction in the risk of disease progression or death. The median overall survival was 46.7 months in the abemaciclib group versus 37.3 months in the placebo group, which translates to a 24% reduction in the risk of death. Abemaciclib also increased the objective response rate (the percentage of patients who had a partial or complete shrinkage of their tumors) from 19.1% to 48.1%.
In the MONARCH 3 trial, abemaciclib plus an aromatase inhibitor (another type of hormone therapy) significantly improved progression-free survival compared to placebo plus an aromatase inhibitor in patients who had not received prior systemic therapy for advanced disease. The median progression-free survival was not reached in the abemaciclib group versus 14.7 months in the placebo group, which translates to a 46% reduction in the risk of disease progression or death. Abemaciclib also increased the objective response rate from 40.2% to 59.2%.
Based on these results, abemaciclib was approved by the US Food and Drug Administration (FDA) in 2017 and by the European Medicines Agency (EMA) in 2018 for the treatment of HR-positive, HER2-negative advanced breast cancer in combination with endocrine therapy after disease progression following endocrine therapy.
However, abemaciclib is not without side effects. The most common adverse events of grade 3 or higher (severe or life-threatening) were diarrhea, neutropenia (low white blood cell count), anemia (low red blood cell count), fatigue, nausea, infections, and liver enzyme elevation . These side effects can be managed with dose adjustments, supportive care, and monitoring.
Abemaciclib is a novel and effective option for patients with HR-positive, HER2-negative advanced breast cancer who have failed previous endocrine therapy. It offers a personalized approach that targets the specific proteins that drive the disease. Abemaciclib represents a breakthrough for this subgroup of patients who have limited treatment options and poor prognosis.
References: : Sledge GW Jr., Toi M., Neven P., et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2019;6(1):116-124. : Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017;35(32):3638-3646.