Introduction

Olaparib (trade name: Lynparza) has been approved in Germany since April 2019 for the treatment of advanced hormone-receptor-negative breast cancer in adults, if the cancer has already spread to other parts of the body or is locally advanced. This drug is a treatment option for people who have a mutated BRCA gene. These people should also have already received treatment with an anthracycline and a taxane drug, if they can tolerate them. People who have hormone-receptor-positive breast cancer should have already had hormone therapy that was ineffective (unless this treatment wasn't an option).

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). This is called advanced breast cancer.

Breast cancer is caused by changes (mutations) in the genes of the cells. In some women the mutations are found in the genes BRCA-1 or BRCA-2. The abbreviation BRCA stands for breast cancer gene.

The growth of tumor cells in breast cancer is influenced by various factors. These include a certain protein on the surface of the cancer cells called the HER2 receptor (human epidermal growth factor receptor). HER2 receptors respond to growth signals and trigger 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. Olaparib has only been approved for the treatment of HER2-negative breast cancer.

Olaparib decreases the production of several proteins that influence tumor growth.

Application

Olaparib is available in the form of tablets, in two doses (100 and 150 mg).

Two 150 mg tablets of olaparib are taken twice a day. The total daily dose is 600 mg of olaparib.

Other treatments

The standard treatment options include capecitabine, vinorelbine, eribulin or treatment with an anthracycline or taxane drug.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) wanted to find out whether olaparib has any advantages or disadvantages compared with the current standard treatments for people who have advanced HER2-negative breast cancer with a BRCA mutation.

The manufacturer provided one suitable study with 302 sets of patient data that could be used in the analysis. In the study, 205 people had treatment with olaparib and 97 people had chemotherapy with capecitabine, vinorelbine or eribulin.

What are the advantages of olaparib?

Life expectancy: The study suggests that olaparib can help patients to live longer if they haven't yet had chemotherapy for their metastatic breast cancer: People who received olaparib passed away after about 23 months on average (median value). People who received the standard treatment passed away after about 15 months on average (median value).

No such difference in life expectancy was found in people who had already had chemotherapy before taking part in the study. They passed away after about 18 months on average (median value), regardless of which treatment they had during the study.

Severe side effects and treatment stopped due to side effects: Early results suggest that olaparib has an advantage here. In the olaparib group, about 38 out of 100 people had severe side effects. About 5 out of 100 people stopped the treatment due to side effects. In the group that had standard treatment, about 50 out of 100 people had severe side effects and about 8 out of 100 people stopped the treatment because of side effects. The severe side effects included severe vascular disease and severe neutropenia, where the body doesn't have enough immune system cells.

Other possible side effects of the treatment include:

  • Hand-foot syndrome (painful swelling and reddening of the palms of the hands and the soles of the feet).The study suggests that olaparib has an advantage here: About 1 out of 100 people who had treatment with olaparib developed hand-foot syndrome, compared to about 21 out of 100 people who were in the other treatment group.
  • Hair loss: Early analyses suggest that olaparib has an advantage here: About 3 out of 100 people in the olaparib group had hair loss (alopecia), compared to about 13 out of 100 people in the other treatment group.
  • General symptoms: Early analyses suggest that general symptoms such as fever and fatigue occured later in the olaparib group than in the standard treatment group.

What are the disadvantages of olaparib?

Severe anemia: Early analyses suggest that olaparib has a disadvantage here: Severe anemia occurred in about 16 out of 100 people in the olaparib group, compared to about 4 out of 100 people who had the standard treatment.

According to early analyses, nausea was more common in people who received olaparib. This problem occurred after about 2 months (median value) in the olaparib group, compared to about 15 months (median value) in the other group.

What remains unanswered?

The study doesn’t include any suitable data concerning the effects of olaparib on the following:

  • Symptoms of the disease
  • Health-related quality of life

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 this review and the hearings received, the G-BA passed a resolution on the added benefit of olaparib (Lynparza).