Introduction

Palbociclib (trade name: Ibrance) has been approved in Germany since November 2016 for the treatment of advanced hormone-receptor-positive breast cancer in women. It is used as a part of anti-hormonal 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.

The growth of tumor cells in breast cancer is influenced by various factors. The drug palbociclib has been approved for use in women with advanced breast cancer whose cancer cells carry receptors for hormones such as estrogen or progesterone. This type of tumor is called hormone-receptor-positive (HR-positive) cancer. In these tumors, hormones such as estrogen or progesterone accelerate the growth of cancer cells.

Palbociclib isn't an option for women whose cancer cells carry the HER2 receptor (human epidermal growth factor receptor).

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

Application

Palbociclib is available in capsule form in three different doses: 75, 100 and 125 mg. One treatment cycle lasts four weeks. In the first three weeks, the drug is taken with a meal once daily at the same time each day. The recommended daily dose is 125 mg. The next cycle starts after a one-week break. Depending on the side effects, stage of the disease, and other treatments, the daily dose can be reduced. Treatment is stopped if the disease progresses or if very severe side effects arise.

Other treatments

If women with advanced HR-positive and HER2-negative breast cancer can’t have chemotherapy, radiotherapy or surgery, the following standard treatments are available:

First-line treatment:

  • Women who have already gone through menopause can use aromatase inhibitors such as anastrozole or letrozole, 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 hormonal treatment was unsuccessful:

  • For women who have already gone through menopause, the options include the drugs tamoxifen, anastrozole, fulvestrant, letrozole, exemestane and everolimus. 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 additional hormonal 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 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of palbociclib compared with the standard treatments for advanced hormone-receptor-positive breast cancer in women.

The manufacturer had already provided IQWiG with data from a study in 2016, and submitted more data from the same study in 2018. This study looked at palbociclib combined with fulvestrant as a subsequent treatment after unsuccessful hormone therapy. But because the treatment it was compared with in the study wasn't suitable for comparison, the study results weren't reliable and couldn't be used in the assessment.

Regarding first-line treatment for women after menopause, IQWiG mainly used one study in 2016 that compared the combination of palbociclib and the aromatase inhibitor letrozole with treatment using letrozole only.

This study involved 666 women. 444 of them received palbociclib and letrozole, while 222 were given letrozole and a placebo (dummy drug). The study showed the following results for these patients:

What are the disadvantages of palbociclib?

  • Severe side effects: The study suggests that palbociclib has a disadvantage here. About 78 out of 100 people who used palbociclib and letrozole had severe side effects, compared to about 25 out of 100 people who used letrozole only. The most common side effects were severe blood disorders and severe lymphatic system disorders. One example is a decrease in the number of white blood cells.

No difference

  • Life expectancy: So far in the study, no difference has been found here between letrozole only and letrozole combined with palbociclib. About 17 to 21 out of 100 women passed away in both groups during an average observation period of about 23 months.
  • Overall health and health-related quality of life: There was no difference here either.
  • Treatment stopped due to side effects: There was also no difference in terms of treatments stopped. In both groups, about 5 to 9 out of 100 women stopped their treatment due to side effects.

What remains unanswered?

  • Symptoms: The manufacturer didn’t provide any suitable data with which to look into this. So it remains unclear whether additional treatment with palbociclib has any advantages or disadvantages here when compared with letrozole only.
  • Progression-free survival: The manufacturer provided data concerning what is known as progression-free survival. Experts use this to determine whether a treatment can stop the cancer from growing. For this purpose, the study mostly used x-ray imaging to evaluate changes in tumors. The hope is that if a tumor stops growing or even shrinks, the woman will live longer as well. However, other cancer treatments have been shown to slow down cancer growth (seen on x-rays) for several weeks or months, but they still didn't prolong life. This goes to show that if you want to assess a medication properly, you also need suitable proof that slowing cancer growth also helps people live longer and improves their quality of life. The data provided by the manufacturer didn't offer enough proof here, though. In women who had treatment with palbociclib, there was no overall difference in terms of number of deaths or health-related quality of life. This suggests that palbociclib doesn't have any noticeable benefits here for these women.

More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the reviews and the hearings received, the G-BA passed a resolution on the added benefit of palbociclib (Ibrance).