The Role of Abemaciclib for HR+, HER2- Metastatic Breast Cancer


Understanding the role of abemaciclib (Verzenio) in managing patients with hormone receptor positive and human epidermal growth factor receptor 2 negative metastatic breast cancer is crucial.

Since approximately a third of patients diagnosed with breast cancer in the United States will eventually progress to the metastatic state, understanding the role of abemaciclib (Verzenio) in managing patients with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) is crucial to approaching treatment for this large subset of patients with breast cancer.

In a session at the Hematology/Oncology Pharmacy Association (HOPA) 2020 Practice Management Virtual Event, Jacob Kettle, PharmD, BCOP, an oncology clinical pharmacy specialist at the University of Missouri Healthcare, explained that in the HR+/HER2- MBC field of oncology, there are a lot of options available for providers to choose from. He noted that such a variety of options is common in the practice of oncology today more generally, which makes it necessary for providers to navigate all of the options available in order to stay abreast of the everchanging landscape of the field.

“What that really requires is for us to abandon some things that are central to human nature. We all demand choice, but the reality is choice is stressful,” said Kettle. “Practicing in oncology today really requires that we abandon preconceived notions because the way you did things yesterday may no longer apply today.”

For example, endocrine therapy has been an essential element of treating patients with HR+/HER2- MBC, but about half of the patients treated with endocrine therapy become resistant to treatment. Kettle noted that this underscores the need for treatment that comes after endocrine therapy. Although chemotherapy has predominantly filled this role, there are new options available now, such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors.

According to Kettle, some really easy markers of poor prognosis that providers can identify are patients who have visceral metastases or patients with rapid progression. These patients may not respond successfully to endocrine therapy alone.

The role of the CDK4/6 inhibitor in treatment of these patients is to end the uninhibited growth of the disease. The CDK4/6 inhibitor abemaciclib not only has this capability, but also has been shown to penetrate the central nervous system at therapeutic levels. This is specifically crucial for treatment because the brain is an important site of the metastatic spread of breast cancer.

In a Monarch 2 trial assessing abemaciclib with fulvestrant in patients with HR+/HER2- MBC, the results demonstrated that abemaciclib with fulvestrant significantly increased median progression-free survival and median overall survival when compared to fulvestrant alone.

In the study, patients with no prior chemotherapy treatment and at least 1 prior endocrine therapy were given either abemaciclib with fulvestrant or a placebo with fulvestrant. Those patients given abemaciclib with fulvestrant had a 49.8% occurrence of events and a median progression free survival (PFS) of 16.4 months, while those given the placebo with fulvestrant had a 70.4% occurrence of events and a PFS of 9.3 months.

In regard to overall survival (OS), patients given abemaciclib with fulvestrant had a 47.3% mortality rate and a median OS of 46.7 months, while those given the placebo with fulvestrant had a 57% mortality rate and a median OS of 37.3 months.

“As clinicians, we want to make sure we’re delivering not just years to patients’ lives, but life to their years,” Kettle said. “Allowing patients to experience more time not on chemotherapy is very meaningful in accomplishing our goal in this disease state, which is giving patients the highest quality of life as we can.”

In a Monarch 3 trial assessing abemaciclib with the aromatase inhibitor anastrozole, the results also showed a significant improvement in median progression-free survival when compared to AI alone as an initial endocrine-based therapy.

In the study, patients with HR+/HER2- iocoregionally recurrent breast cancer or MBC with no prior treatment for MBC were given either abemaciclib with anastrozole or a placebo with anastrozole. The percentage of events was 42.1% for patients given abemaciclib with anastrozole and 65.5% for patients given a placebo with anastrozole. Additionally, the PFS for abemaciclib with anastrozole was 28.2 months, while the PFS for a placebo with anastrozole was 14.8 months.

“The result here again is that we have, by adding Verzenio to the aromatase inhibitor, effectively doubled progression-free survival,” Kettle said.

Since both of these studies included a fairly representative sample of patients, Kettle noted that an important question was how those patients with negative risk factors performed. After pulling out these patients with negative risk factors from both studies, Kettle explained that the answer was quite clear.

“Those patients with primary resistance still did significantly better when you add Verzenio,” Kettle said. “If you select out these specific patients, they are not still benefitting as much as those without the risk factors, but we’ve delivered improved outcomes for those patients, and I think that’s really critical to understand.”


Kettle J. A CDK 4 & 6 Inhibitor With Overall Survival Data for Women With HR+, HER2- Metastatic Breast Cancer, Including Those Likely To Do Worse. Paper presented at: HOPA 2020 Practice Management; September 11, 2020; virtual. Accessed September 11, 2020.

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