FDA Approval: Abemaciclib (Verzenio) for Breast Cancer

What happened on 28 September 2017

The FDA approved abemaciclib, sold as Verzenio, for some people with advanced or metastatic breast cancer. NCI reported the approval that October.

Two uses were approved at once. The first was abemaciclib with fulvestrant, a hormone drug, for hormone receptor (HR)-positive, HER2-negative breast cancer that had grown despite hormone therapy. The second was abemaciclib on its own, for women and men who had already had both hormone therapy and chemotherapy after their cancer spread.

NCI noted why the second one mattered. Abemaciclib was the third CDK4/6 inhibitor to reach the market. It was the first approved to be taken alone.

Approval at a glance

Field	Detail
Drug	Abemaciclib (Verzenio)
Application	NDA 208716
Regulator	FDA
Date	28 September 2017
Class	CDK4/6 inhibitor
Cancer	HR-positive, HER2-negative advanced or metastatic breast cancer
Form	Tablet, taken by mouth twice a day

Why the receptor status is the whole story

Two letters on a pathology report decide whether this drug is even a question. HR-positive means the cancer cells carry receptors for estrogen or progesterone, so hormones feed their growth. HER2-negative means they do not overproduce the HER2 protein.

If a report says otherwise, the 2017 approval does not describe that cancer. Our page on biomarker testing explains where those results come from.

How a CDK4/6 inhibitor works

Cell division runs through a series of checkpoints. Two proteins, CDK4 and CDK6, help push a cell past one of them.

In HR-positive breast cancer, hormone signals are what drive that machinery. Hormone therapy cuts the signal. A CDK4/6 inhibitor jams the machine further down the line.

That is why these drugs are usually given with hormone therapy rather than instead of it. The two block the same process at different points.

The trials the approval rested on

NCI reported that both trials were funded by the manufacturer, Eli Lilly.

MONARCH 2 supported the fulvestrant combination. About 670 women were randomly assigned to fulvestrant with abemaciclib or fulvestrant with placebo. Median progression-free survival — the time before the cancer grew again — was 16.4 months with abemaciclib and 9.3 months without. That was the trial's main measure.

MONARCH 1 supported taking the drug alone. It was a phase 2 study of 132 patients, and everybody in it received abemaciclib. There was no comparison group.

A third trial, MONARCH 3, tested the drug as a first treatment for advanced disease. NCI reported that 493 postmenopausal women were randomly assigned to abemaciclib or placebo, each with an aromatase inhibitor. Progression-free survival was substantially longer with abemaciclib, and 59% of tumors shrank compared with 44% on placebo.

Note what all of that measures. Time before the cancer grew, and how often tumors shrank. Neither is a statement that people lived longer. Our explainer on clinical trial phases covers why those endpoints are used and what they leave open.

How the label has grown since

The current FDA label is wider than the 2017 approval. It now also covers abemaciclib with an aromatase inhibitor as the first endocrine-based treatment for advanced or metastatic HR-positive, HER2-negative disease.

It also covers a different situation entirely: abemaciclib with endocrine therapy, either tamoxifen or an aromatase inhibitor, after surgery for HR-positive, HER2-negative, node-positive early breast cancer at high risk of coming back. That is treatment aimed at cure rather than control, and it is a use the 2017 approval did not include.

What taking it involves

Abemaciclib is a tablet taken twice a day, every day, with no week off. That continuous schedule is part of why its side effect profile differs from the other drugs in its class.

Diarrhea is the one to plan for. NCI reported it as the most frequent side effect across the abemaciclib trials. The FDA label instructs patients to start antidiarrheal medicine at the first sign of loose stools, drink more fluids, and tell their care team. Most teams send people home with that medicine before it is needed.

The label sets out a monitoring schedule for two other problems. Blood counts are checked before starting, every two weeks for the first two months, monthly for the next two, and after that as needed — because the drug can drop neutrophils, the white cells that fight bacteria. Liver function tests follow the same rhythm.

Three further warnings sit on the label. Interstitial lung disease and pneumonitis, meaning inflammation of lung tissue, where the label records severe and fatal cases and instructs stopping the drug permanently for severe ones. Blood clots in veins and lungs. And harm to a developing fetus.

What this does and doesn't change

For advanced HR-positive, HER2-negative breast cancer, this added a daily tablet that roughly doubled the time before the cancer grew when paired with fulvestrant. It was also the first drug of its class that could be taken on its own.

It is not chemotherapy, it is not a cure, and it has no role in HER2-positive or triple-negative disease. Our guides to breast cancer and hormone therapy cover the background.

What to keep in perspective

• Longer time before the cancer grows is a real benefit, and it is not the same measure as living longer. The 2017 approval did not rest on survival data.
• MONARCH 1 had no control group, so its results cannot tell you how those patients would have done on something else.
• Both approval trials were funded by the company that makes the drug. That is normal and it is worth knowing.
• Labels move. What the drug is approved for today is broader than what it was approved for in 2017, and it may change again.

Questions worth asking

• Does my report say HR-positive and HER2-negative, and where does this fit with my prior treatments?
• What is the plan for diarrhea, and at what point should I call?
• How will we know whether it is working, and what happens if it stops?

Sources

• NCI Cancer Currents: Abemaciclib Approved by FDA for Advanced or Metastatic Breast Cancer
• FDA prescribing information: VERZENIO (abemaciclib) tablets
• FDA Drugs@FDA overview: VERZENIO, NDA 208716
• NCI drug information: Abemaciclib

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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