Introduction

Ribociclib (trade name: Kisqali) has been approved in Germany since August 2017 for the treatment of 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 anti-hormonal therapy in combination with an aromatase inhibitor or the anti-estrogen drug fulvestrant. Ribociclib is an option for both first-line anti-hormonal therapy as well as second-line therapy if previous anti-hormonal therapy was unsuccessful. In women before and during menopause, ribociclib is combined with a GnRH analogue.

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. Ribociclib is approved only for the treatment of HER2-negative breast cancer.

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

Application

Ribociclib is available in the form of 200 mg tablets. One treatment cycle lasts four weeks. In the first three weeks, the drug is taken once daily at the same time each day, ideally in the morning. The recommended daily dose is 600 mg (three 200 mg tablets). The next cycle starts after a one-week break.

If there are severe side effects, the dose can be reduced or treatment can be interrupted. The treatment is stopped if the cancer continues to get worse or if severe side effects arise.

Ribociclib is combined with an aromatase inhibitor such as letrozole or with the anti-estrogen drug fulvestrant.

In women before and during menopause, ribociclib is also combined with a GnRH analogue.

Other treatments

The following standard treatments are available for advanced hormone-receptor-positive and HER2-negative breast cancer in women:

First-line anti-hormonal therapy:

  • After menopause aromatase inhibitors such as anastrozole or letrozole or the anti-estrogen drug fulvestrant, which block hormone production, can be used. If these medications aren't suitable, tamoxifen is an option.
  • Before and during menopause tamoxifen can be used. In addition, the production of hormones is blocked by medication.

Second-line or subsequent therapy if previous anti-hormonal therapy was unsuccessful:

  • After 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.
  • Before and during menopause various anti-hormonal cancer treatments can be used. The treatment is chosen depending on factors such as which have been tried before. It is individually adjusted by the doctor. Possible treatments include tamoxifen, letrozole, exemestane, megestrol acetate and medroxyprogesterone acetate.

Assessment

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

The manufacturer did not provide any suitable data related to the following situations:

  • Ribociclib as part of first-line anti-hormonal therapy in women before and during menopause
  • Ribociclib as part of second-line anti-hormonal therapy in women after menopause: The manufacturer did provide one study comparing the combination of ribociclib and fulvestrant with treatment with fulvestrant alone. In this study, fulvestrant was not used in the way for which it has been approved, though.

Suitable data was provided for the following situations: 

  • Ribociclib (Kisqali) as part of first-line anti-hormonal therapy in women after menopause
  • Ribociclib (Kisqali) as part of second-line anti-hormonal therapy in women before and during menopause

Learn more

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 ribociclib (Kisqali).