Introduction

Pembrolizumab (trade name: Keytruda) has been approved in Germany since March 2019 for the first-line treatment of metastatic non-small-cell lung cancer in combination with chemotherapy.

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

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

Depending on the result of a tissue examination, non-small-cell carcinomas are further classified into these types:

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Large-cell carcinoma

NSCLC is 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) through the blood or lymphatic system. This is called metastatic lung cancer.

Those who are affected might have a mutated receptor in the tumor tissue called an epidermal growth factor receptor (EGFR). The tumor cells may also produce an enzyme called anaplastic lymphoma kinase (ALK). Both of these changes cause further uncontrolled tumor growth. The tumor may also produce the protein PD-L1. Experts distinguish between tumors in which at least 50% of tumor cells contain PD-L1 (PD-L1 positive) and tumors in which less than 50% of tumor cells contain PD-L1 (PD-L1 negative).

PD-L1 weakens the body's immune response against the tumor cells, particularly the activity of T cells.

Pembrolizumab blocks the effect of PD-L1 produced by the tumor tissue and stimulates the immune system to fight the cancer cells in order to inhibit tumor growth.

Application

Pembrolizumab comes in the form of a powder that is dissolved in a liquid and then given through an infusion (an IV drip), entering the bloodstream directly through a vein. This takes about 30 minutes. The drug is given every three weeks at a dose of 200 mg. This treatment is stopped if severe side effects occur or if the cancer continues to progress.

Other treatments

The following treatment options are available for people with metastatic lung cancer who have not had treatment before, depending on the tumor type:

  • For a PD-L1 negative, non-squamous NSCLC without a mutated EGFR or ALK-positive mutation, the options are cisplatin in combination with vinorelbine, gemcitabine, docetaxel, paclitaxel or pemetrexed. If the tumor is PD-L1 positive, pembrolizumab is used alone.
  • For a PD-L1 negative, squamous NSCLC, the options are cisplatin or carboplatin in combination with vinorelbine, gemcitabine, docetaxel or paclitaxel. Another treatment option is carboplatin in combination with nab-paclitaxel. If the tumor is PD-L1 positive, pembrolizumab is used alone.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of pembrolizumab in combination with chemotherapy compared with the standard treatments for metastatic lung cancer in adults.

The manufacturer provided a total of three usable studies for the following groups:

  • Pembrolizumab with chemotherapy for people with PD-L1 negative, non-squamous metastatic lung cancer
  • Pembrolizumab with chemotherapy for people with PD-L1 negative, squamous metastatic lung cancer

For two further groups of patients, the manufacturer provided studies for an indirect comparison:

  • People with PD-L1 positive, non-squamous metastatic NSCLC without a mutated EGFR or ALK-positive mutation
  • People with PD-L1 positive, squamous metastatic NSCLC

Indirect comparisons involve two studies (in the simplest case): One study compares medication A with medication X. The other compares medication X with the standard treatment. Then the results for medication A from the first study are compared with the results for the standard treatment from the second study. The results of this kind of comparison are generally less reliable than those of a direct comparison.

The studies provided by the manufacturer were questionable because important data such as information on life expectancy, symptoms, severe side effects, or health-related quality of life were not suitable for analysis. So it isn't possible to draw a final conclusion on the advantages or disadvantages of pembrolizumab in combination with chemotherapy compared with the standard treatments for the above-mentioned groups.

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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 pembrolizumab (Keytruda) for the treatment of non-squamous NSCLC and squamous NSCLC.