Trastuzumab emtansine (Kadcyla) for the treatment of early-stage breast cancer

Introduction

Trastuzumab emtansine (trade name: Kadcyla) has been approved in Germany since 2014 for the treatment of advanced or metastatic breast cancer. As of December 2019, trastuzumab emtansine is also approved for the adjuvant treatment of HER2-positive early-stage breast cancer in adults. Because men can also get breast cancer, it is an option for both men and women who had chemotherapy with a taxane and an anti-HER2 therapy (such as trastuzumab) before having surgery. The tumor was removed completely in these patients, but active cancer cells were still found in the removed tissue.

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” breast cancer. HER2-positive breast cancer grows relatively fast, and recurrences are more likely.

Trastuzumab is an antibody that binds to the HER2-receptor and blocks it, which is believed to inhibit the growth of the cancer cells. The drug emtansine is attached to the antibody trastuzumab so that it can target and kill cancer cells.

Application

Trastuzumab emtansine is given as an infusion (IV drip), entering the bloodstream directly through a vein. The infusion takes about 90 minutes. The exact dose will depend on the patient's body weight.

The treatment is given a total of 14 times, with a break of 3 weeks between each infusion. It should be stopped if the disease progresses or if very severe side effects arise.

Other treatments

Patients who have HER2-positive early-stage breast cancer continue with the anti-HER2 treatment with trastuzumab for a total of one year after chemotherapy and surgery. They may also have hormone therapy or additional radiotherapy.

Assessment

In 2020, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of trastuzumab emtansine compared to the standard treatments for HER2-positive early-stage breast cancer in people who still have the cancer after chemotherapy and surgery.

The manufacturer provided one study involving about 1,500 people (including a few men). One half of the people were given treatment with trastuzumab emtansine, while the other half received trastuzumab.

The study showed the following:

What are the advantages of trastuzumab emtansine?

Recurrences: The study suggests that trastuzumab emtansine can lower the likelihood that the cancer will return (recurrences): About 13 out of 100 people who were given trastuzumab emtansine had a recurrence, compared to about 23 out of 100 people who received trastuzumab.

What are the disadvantages of trastuzumab emtansine?

Symptoms of the disease: Early results suggest that loss of appetite and constipation during the treatment were more common in people who had trastuzumab emtansine than they were in people who used trastuzumab:

  • Loss of appetite: Loss of appetite occurred in about 19 out of 100 people who had treatment with trastuzumab emtansine, but only in about 11 out of 100 people in the comparison group.
  • Constipation: Constipation occurred in about 30 out of 100 people who had treatment with trastuzumab emtansine, but only in about 18 out of 100 people in the comparison group.

Health-related quality of life: Early results suggest that trastuzumab emtansine also has a disadvantage compared to trastuzumab in some aspects of health-related quality of life. During the study, the people who were given trastuzumab emtansine felt more restricted in terms of physical activities of daily life such as shopping or personal hygiene (physical functioning), as well as their family life and social activities (social functioning).

Patients aged 65 and over who were given trastuzumab emtansine assessed their health and quality of life as poorer compared to the patients who had trastuzumab.

Severe side effects: The study suggests that severe side effects are more common with trastuzumab emtansine: About 26 out of 100 people who had treatment with trastuzumab emtansine developed severe side effects, compared to only about 15 out of 100 people who were given trastuzumab.

These severe side effects included the following:

  • Gastrointestinal diseases: About 3 out of 100 people who had treatment with trastuzumab emtansine developed severe gastrointestinal (stomach and bowel) diseases, compared to only about 1 out of 100 people in the comparison group.
  • Neuropathy (problems affecting the nerves): Bei About 1 out of 100 people who had treatment with trastuzumab emtansine developed neuropathy. This side effect didn’t occur in the comparison group. In peripheral neuropathy, nerves in the body that aren't part of the brain or spinal cord (peripheral nerves) are damaged. This can lead to symptoms such as abnormal sensations, pain, partial paralysis, weakness or dizziness.
  • Lower number of platelets in the blood: About 6 out of 100 people who were given trastuzumab emtansine had a much lower count of platelets (thrombocytes) in their blood. This side effect occurred in less than 1 out of 100 people in the comparison group.
  • Infection: About 5 out of 100 people who had treatment with trastuzumab emtansine developed a severe , compared to only about 3 out of 100 people in the comparison group.

Early results suggest that trastuzumab emtansine has a disadvantage compared to trastuzumab regarding further side effects too, including:

  • Tiredness
  • Fever
  • Nausea and vomiting
  • Constipation
  • Dry mouth
  • Inflammation of the mucous membranes lining the mouth (stomatitis)
  • Headaches
  • Diseases affecting the airways and eyes

Treatment stopped due to side effects: Early results suggest that treatments with trastuzumab emtansine are stopped more often due to side effects than treatments with trastuzumab are: About 18 out of 100 people who used trastuzumab emtansine stopped their treatment, compared to only about 2 out of 100 people who received trastuzumab.

No difference

Life expectancy: There was no difference between the two treatment groups here.

Symptoms of the disease: There were no relevant differences in terms of these side effects. These include:

  • Exhaustion
  • Nausea and vomiting
  • Breathing problems
  • Trouble sleeping
  • Diarrhea
  • Pain

Severe heart problems: At most, 1 out of 100 people were affected by this severe side effect in each group.

Health-related quality of life: There was no difference in other aspects of health-related quality of life, such as how well people were able to concentrate or remember (cognitive functioning), how they assessed their future (future perspectives), whether they felt limited in their everyday life, their free time or their work (role functioning) or how agitated or depressed they felt (emotional functioning).

General health: The patients in the study were asked how they would assess their overall health. There was no difference between the groups here.

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 trastuzumab emtansine (Kadcyla).

Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Trastuzumab emtansine (breast cancer) – Benefit assessment according to §35a Social Code Book V. Dossier assessment; Commission A20-07. April 14, 2020. (IQWiG reports; Volume 900).

IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

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Created on May 7, 2020
Next planned update: 2023

Authors/Publishers:

Institute for Quality and Efficiency in Health Care (IQWiG, Germany)

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