Introduction

Neratinib (trade name: Nerlynx) has been approved in Germany since August 2018 for the extended adjuvant treatment of hormone-receptor-positive, HER2-amplified early-stage breast cancer in adults. This medication is an option for people who have completed adjuvant treatment with trastuzumab following breast cancer surgery. No more than one year may have passed since the treatment with trastuzumab.

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 especially high numbers of these receptors on the breast cancer cells, the cancer is called “HER2-positive,” or “HER2-amplified.” HER2-positive breast cancer grows relatively fast, and recurrences are more likely.

About two thirds of all women with breast cancer have a hormone-sensitive tumor. This means that hormones like estrogen influence how fast the cancer cells grow. If the cancer cells have receptors that the hormones can attach to, the tumor is referred to as hormone-receptor-positive breast cancer (HR-positive or HR+).

Both neratinib and trastuzumab bind to the HER2 receptors, blocking them. This is thought to inhibit the growth of the cancer cells.

Application

The drug is available in the form of 40 mg tablets.

The recommended dose is 240 mg once a day – the equivalent of 6 tablets, each containing 40 mg of neratinib. It is taken with a meal, preferably in the morning. The recommended total treatment duration is one year.

Treatment with neratinib also needs to start within one year of the completion of the treatment with trastuzumab.

Other treatments

“Watchful waiting” is an option for people who have hormone-receptor-positive, HER2-amplified early-stage breast cancer who completed adjuvant treatment with trastuzumab less than one year ago. This is an approach that involves not continuing with any treatment and instead checking regularly to find out early enough whether the cancer has come back so that it can be treated. Any new symptoms will be investigated. Treatment decisions are made together with the doctor.

Assessment

In 2020, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether neratinib has any advantages or disadvantages compared to the standard treatment when used in the extended adjuvant treatment of hormone-receptor-positive, HER2-amplified early-stage breast cancer in women who completed adjuvant treatment with trastuzumab less than one year ago.

The manufacturer provided one suitable study with 1,334 sets of patient data that could be used in the analysis. All of the study participants were following the watchful waiting approach. In addition, neratinib was given to 670 of the women and a placebo (fake medication) was given to 664 of them.

What are the advantages of neratinib?

Recurrence: Early analyses suggest that neratinib has an advantage here. Within around 2 years, the cancer came back (recurrence) in about 2 out of 100 women who were given neratinib – compared to about 9 out of 100 women who did not receive neratinib.

What are the disadvantages of neratinib?

Severe side effects: The study suggests that neratinib has a disadvantage here: Severe side effects started within nearly 9 weeks on average (median value) during treatment with neratinib. As expected, patients who were not given neratinib didn’t have any severe side effects even after one year on average (median value).

The severe side effects included:

  • Gastrointestinal (stomach and bowel) problems: The study suggests that neratinib has a disadvantage here: In the study, about 42 out of 100 women developed gastrointestinal problems during the treatment with neratinib – compared to about 2 out of 100 women who did not use neratinib. These severe gastrointestinal problems included severe diarrhea. Severe diarrhea occurred in about 39 out of 100 women who used neratinib, compared to about 1 out of 100 women who did not receive neratinib.
  • Exhaustion: Based on initial analyses, about 2 out of 100 women who were given neratinib were affected by exhaustion, while none of the women who did not use neratinib experienced this problem.
  • Nutritional and metabolic disorders: Initial analyses also suggest that neratinib has a disadvantage here. About 3 out of 100 women who were given neratinib developed nutritional and metabolic disorders, while only 1 to 2 out of 100 women who did not use neratinib had this kind of disorder.
  • Disorders of the nervous system: Initial analyses suggest that neratinib has a disadvantage here. About 3 out of 100 women who were given neratinib developed disorders of the nervous system, compared to about 1 out of 100 women who did not receive it.

The study also suggested that neratinib had a disadvantage in terms of the side effects muscle cramps and skin problems.

Treatment stopped due to side effects: Initial analyses suggest that neratinib has a disadvantage here too. In the study, about 27 out of 100 patients who were given neratinib stopped their treatment, compared to only about 5 out of 100 patients who did not use neratinib.

No difference

There was no difference between the groups in terms of overall health or health-related quality of life.

What remains unanswered?

Life expectancy: The manufacturer didn’t provide any data on this matter.

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 neratinib (Nerlynx).