Introduction

Osimertinib (trade name: Tagrisso) has been approved in Germany since March 2016 for the treatment of advanced lung cancer with a T790M mutation of the epidermal growth factor receptor (EGFR). It can be used in adult patients who have cancer cells with particular mutations that can lead to faster tumor growth.

Since June 2018, osimertinib has also been approved for the first-line treatment of advanced lung cancer with activating mutations of the epidermal growth factor receptor. Learn more about advantages and disadvantages of osimertinib for this group of people here.

Lung cancer is caused by the malignant growth of cells in the airways (bronchi). It is also referred to as a bronchogenic carcinoma. There are two main types of tumors:

  • small-cell lung cancer (SCLC) and
  • non-small-cell lung cancer (NSCLC).

NSCLC is surgically removed. 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. It is then called advanced lung cancer.

Some people with non-small-cell-lung cancer have an abnormal protein in the tumor tissue, called epidermal growth factor receptor (EGFR). The mutated receptor may lead to uncontrolled growth of the tumor. In this case, drugs are often used to block the mutated receptor. These medications are called EGFR tyrosine kinase inhibitors (EGFR TKIs). They are less effective in patients who have one particular mutation, known as the T790M mutation.

Osimertinib aims to block the mutated receptor in patients who have a T790M mutation in particular, in order to inhibit further tumor growth.

Application

Osimertinib is taken once a day in tablet form. The drug is available in two different doses: 40 and 80 mg. The recommended dose is 80 mg per day.

The dosage depends on how well the patient tolerates the drug, as well as on the side effects, and can be adjusted individually. The treatment is stopped if the disease still progresses or if very severe side effects arise.

Other treatments

Adults with a T790 mutation who have not had treatment yet or who have only had platinum-based chemotherapy, the drug treatment options include gefitinib, erlotinib, gemcitabine, vinorelbine or a combination of cisplatin or carboplatin and another cytostatic drug. For patients who have had platinum-based chemotherapy, best supportive care (BSC) may also be an option in some circumstances instead of further treatment with cytostatics. Supportive care should be tailored to individual needs, relieve symptoms such as pain, and improve quality of life.

Cytotoxic chemotherapy is the standard treatment for adults with a T790M mutation who have already had treatment with an EGFR TKI. If this is not an option, BSC is used.

Assessment

In 2016 and 2017, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether osimertinib has any advantages or disadvantages compared with the standard treatments for adults with advanced lung cancer and a T790M mutation.

In 2017, the manufacturer provided data from one study that offered at least preliminary answers to a number of questions. The study involved adults with a T790M mutation who had previously had treatment with an EGFR TKI and were able to have cytotoxic chemotherapy. Despite the advanced stage of their condition, the patients were in good general health. The researchers at IQWiG analyzed data from 132 patients. 87 people had treatment with osimertinib, the other 45 received combined chemotherapy (cisplatin and pemetrexed). The following results apply only to this group.

What are the advantages of osimertinib?

  • Exhaustion, trouble breathing and insomnia: According to preliminary estimates, osimertinib led to a greater improvement in these symptoms during the course of the study than the standard treatment did.
  • Nausea, vomiting and loss of hair: The study suggests that osimertinib has an advantage over combined chemotherapy in terms of these symptoms as well.
  • Health-related quality of life: The study also suggests that osimertinib has an advantage regarding some aspects of quality of life, including:
    • Physical functioning: Compared to patients who had the standard treatment, those who had treatment with osimertinib were better able to manage everyday activities such as grocery shopping, eating or doing the laundry.
    • Role functioning: Compared to patients who received cisplatin and pemetrexed, those who had treatment with osimertinib felt less restricted by their disease in their everyday life, social activities or work.
    • Social functioning: Compared to those who had combined chemotherapy, the patients who took osimertinib felt less limited in activities with their family and friends, and other social activities.
  • The two treatments were not found to differ in terms of their effects on other aspects of health-related quality of life such as concentration, memory or mood.
  • Severe side effects: According to preliminary estimates, severe side effects were less common in people who took osimertinib than in people who had combined chemotherapy.

What are the disadvantages of osimertinib?

The study did not find that osimertinib had any disadvantages compared with combined chemotherapy.

No differences

There was no difference between the two treatments in terms of the following aspects:

  • Life expectancy
  • Pain, nerve inflammations and coughing up blood
  • Loss of appetite, constipation, diarrhea and difficulties swallowing
  • General health
  • Treatment stopped due to side effects

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 osimertinib (Tagrisso).