Introduction

Ramucirumab (trade name: Cyramza) has been approved in Germany since January 2020 for the treatment of metastatic non-small-cell lung cancer in adults. The drug can be used in adults who have cancer cells with particular mutations that lead to faster tumor growth. When used in first-line treatment, ramucirumab is combined with erlotinib.

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 lung cancer:

  • Small-cell lung cancer (SCLC)
  • Non-small-cell lung cancer (NSCLC)

NSCLC is surgically removed, if possible. Sometimes it has already spread through the blood or lymphatic system and formed tumors in other parts of the body. These are called metastatic tumors or metastases. If this has happened, the cancer is considered to be advanced lung cancer. A full recovery is then no longer possible. Treatment then aims to stop the cancer from getting worse for as long as possible and reduce the symptoms.

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. There are a number of different mutations, such as L858R or del19.

The drug ramucirumab is an antibody that disrupts the formation of new blood vessels. This is believed to prevent the tumor from growing any more, stopping the disease from progressing.

Application

Ramucirumab is given through a drip (infusion) every 2 weeks. Each infusion takes about 60 minutes. The dose is based on body weight and can be adjusted if side effects occur. Treatment is stopped if the tumor continues to grow or ramucirumab is no longer tolerated. When used in the first-line treatment of metastatic non-small-cell lung cancer, ramucirumab is combined with the drug erlotinib.

Other treatments

For patients with metastatic non-small-cell lung cancer with the EGFR mutations L858R or del19, the drugs afatinib, gefitinib, erlotinib or osimertinib are treatment options.

For patients with other EGFR mutations, individually tailored treatment is an option. This treatment then depends on which EGFR mutations there are. It is individually modified by the doctor. The medication options include afatinib, cisplatin or carboplatin.

Assessment

In 2020, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether ramucirumab has any advantages or disadvantages compared to other first-line treatments for metastatic non-small-cell lung cancer.

The manufacturer provided some initial results of one stilll ongoing study involving about 450 people whose tumor had a L858R or del19 mutation of the EGFR gene. One half of the participants in this study were given ramucirumab, and the other half received a placebo (fake treatment). All of the patients were also given erlotinib.

What are the advantages of ramucirumab?

Ramucirumab with erlotinib didn’t have any advantages compared to a placebo with erlotinib.

What are the disadvantages of ramucirumab?

Severe side effects overall: The study suggests that severe side effects were more common in people who took ramucirumab. About 72 out of 100 people who took ramucirumab plus erlotinib had serious side effects, compared with only 54 out of 100 people who used the placebo plus erlotinib.

These serious side effects included:

  • Severe diarrhea: Vomiting occurred in about 7 out of 100 people who had treatment with ramucirumab and erlotinib, but only in about 1 out of 100 people in the group that was given a placebo and erlotinib.
  • Severe high blood pressure: About 24 out of 100 people who had treatment with ramucirumab and erlotinib developed severe high blood pressure, compared to about 5 out of 100 people in the comparison group who had a placebo and erlotinib.
  • Severe infections and parasitic diseases: About 17 out of 100 people who had treatment with ramucirumab and erlotinib developed a severe infection, compared to about 7 out of 100 people in the comparison group.

Other side effects included edemas in the arms or legs. The study suggests that ramucirumab has a disadvantage here too when combined with erlotinib. While about 23 out of 100 people in that group had edemas, only about 4 out of 100 people who were given a placebo in combination with erlotinib did.

No difference

Life expectancy: There was no difference here between the treatments after an average (median value) of 20 months. About 17 to 19 out of 100 people in each group passed away.

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

  • Symptoms of the disease
  • General health
  • Treatment stopped due to side effects

What remains unanswered?

It’s not possible to tell which advantages and disadvantages ramucirumab has for patients with other EGFR mutations based on the data submitted by the manufacturer.

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 ramucirumab (Cyramza).