Introduction

Abemaciclib (trade name EU: Verzenios, U.S.: Verzenio) has been approved in Germany since September 2018 for the treatment of advanced hormone-receptor-positive breast cancer in women, if the cancer has already spread to other parts of the body or is locally advanced. It is used as a part of antihormonal therapy in combination with an aromatase inhibitor or the anti-estrogen drug fulvestrant.

Breast tumors are surgically removed, if possible. But sometimes the tumor has already become too large or the cancer has spread to other parts of the body (metastasis) through the blood or lymphatic system. This is called advanced breast cancer.

One factor affecting the speed at which breast cancer cells spread is whether they have receptors for hormones such as estrogen or progesterone. If they do, the tumor is called hormone-receptor-positive (HR-positive) cancer. In these tumors, hormones such as estrogen or progesterone accelerate the growth of cancer cells.

A certain protein on the surface of the cancer cells, called the HER2 receptor (human epidermal growth factor receptor 2), also reacts to growth signals and accelerates tumor growth. If there are a smaller number of these receptors on the cells of a breast tumor, it is called HER2-negative breast cancer. HER2-negative breast cancer grows relatively slowly. Abemaciclib isn't an option for women whose cancer cells carry the HER2 receptor (HER2-positive breast cancer).

Abemaciclib inhibits cell division in the cancer cells, slowing down tumor growth.

Application

Abemaciclib is available in the form of tablets, in three different doses: 50, 100 and 150 mg. The recommended dose is 150 mg twice a day.

The dose depends on how well the patient tolerates the drug, as well as on the side effects, and can be adjusted individually.

Other treatments

For women with advanced hormone-receptor-positive and HER2-negative breast cancer, the following standard treatments are available:

First-line antihormonal treatment:

  • Women who have already gone through menopause can use aromatase inhibitors such as anastrozole or letrozole or the anti-estrogen drug fulvestrant, which block hormone production. If these medications can’t be used, tamoxifen is an option.
  • Women who haven’t yet gone through menopause, or who are still going through menopause, can use tamoxifen. Menopause is then also induced with medication.

Subsequent treatment if previous antihormonal treatment was unsuccessful:

  • For women who have already gone through menopause, the options include the drugs tamoxifen, anastrozole, fulvestrant, letrozole, exemestane, or a combination of everolimus and exemestane. The choice of drug will depend on previous treatments and the stage of the disease.
  • Women who haven’t yet gone through menopause, or who are still going through menopause, can have antihormonal treatment to fight the cancer. This is chosen depending on factors such as which treatments have been tried before. The treatment is individually modified by the doctor.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of abemaciclib in combination with an aromatase inhibitor compared with the standard treatments for women with advanced hormone-receptor-positive and HER2-negative breast cancer.

The manufacturer provided one study. The study looked at abemaciclib as part of first-line antihormonal treatment for women after menopause. Out of a total of 493 participants, 328 women received abemaciclib combined with either anastrozole or letrozole, and 165 women received anastrozole or letrozole combined with a placebo (fake medication). The study showed the following results for these patients:

What are the advantages of abemaciclib?

The study did not find that adding abemaciclib to the standard treatment had any advantages.

What are the disadvantages of abemaciclib?

  • Diarrhea: Initial analyses suggest that abemaciclib has a disadvantage here.
  • Severe side effects: The study suggests that adding abemaciclib to the treatment has disadvantages here, too. In the group that had additional treatment with abemaciclib, about 62 out of 100 women experienced severe side effects. This was the case in about 26 out of 100 women who had the standard treatment.
  • The possible severe side effects include severe neutropenia: Neutropenia means a lack of immune system cells. The study suggests that this side effect occurs more often if abemaciclib is added to the treatment. In the group that had additional treatment with abemaciclib, about 24 out of 100 women experienced neutropenia. This happened in about 1 out of 100 women who had the standard treatment.
  • Treatment stopped due to side effects: The study suggests that abemaciclib has a disadvantage here: About 25 out of 100 women who had additional treatment with abemaciclib stopped their treatment due to the side effects. This was the case in about 4 out of 100 women who had the standard treatment.

No differences

  • Life expectancy: There was no difference between the two treatment groups here.
  • Symptoms: There was also no difference between the two treatment groups in terms of various symptoms of the disease:
    • Fatigue
    • Nausea and vomiting
    • Loss of appetite
    • Pain
    • Shortness of breath
    • Sleep problems
    • Constipation
    • Symptoms affecting the breast and arms
  • General health: There was no difference between the treatment groups here.
  • Health-related quality of life: There was no relevant difference regarding quality of life either.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of abemaciclib (EU: Verzenios, U.S.: Verzenio).