Introduction

Pembrolizumab (trade name: Keytruda) has been approved in Germany since September 2018 for the treatment of squamous cell carcinoma of the head and neck in adults whose cancer has come back (recurrence) or spread (metastasis). Pembrolizumab is a treatment option if the tumor cells have a particular mutation that leads to a reduced immune system reaction and if platinum-based chemotherapy is not effective enough.

Squamous cell carcinomas of the head and neck include tumors in the following areas:

  • Mouth
  • Throat
  • Larynx (voice box)
  • Nose and sinuses
  • Neck
  • Thyroid gland

They usually develop in the skin or mucous membranes and are caused by malignant changes of the upper skin cells (squamous cells).

The symptoms can vary a lot, depending on the location of the tumor. Tumors in the mouth usually cause swellings or ulcers, while tumors in the throat often cause trouble swallowing. Tumors of the larynx may lead to chronic hoarseness or a feeling of having a foreign object in the throat. Head and neck cancer is more common in older people over the age of 60.

Some tumors of the head and neck have higher levels of the protein PD-L1 in them. This protein weakens the body's immune response against the tumor cells.

Pembrolizumab is meant to inhibit tumor growth by blocking the effect of the PD-L1 protein produced by the tumor tissue.

Application

Pembrolizumab is given every three weeks through an intravenous drip (infusion), at a dose of 200 mg. The infusion takes about 30 minutes.

This treatment is stopped if severe side effects occur or if the cancer continues to progress.

Other treatments

The treatment options for adults with squamous cell carcinoma of the head and neck who have had treatment before include individually adjusted treatments with medication (e.g. chemotherapy with methotrexate) or radiation therapy. Surgery is also an option.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether pembrolizumab has any advantages or disadvantages compared with individual treatment for people with advanced squamous cell carcinoma of the head and neck with elevated levels of PD-L1 who have had treatment before. The manufacturer gave IQWiG one study involving a small number of participants (37 people) that provided at least preliminary answers to some questions. 16 people had treatment with pembrolizumab, and another 21 were given methotrexate. Despite the advanced stage of the disease, all patients involved were otherwise in good general health. This is what was found:

What are the advantages of pembrolizumab?

Life expectancy: The study suggests that pembrolizumab has an advantage here: People in the pembrolizumab group passed away within 17 months on average (median value), while those in the methotrexate group already passed away after an average of only 6 months.

What are the disadvantages of pembrolizumab?

Immune-mediated side effects: Immune-mediated side effects are medical conditions in which someone’s immune system attacks their own body. The study suggests that pembrolizumab has a disadvantage here. These side effects typically occurred after about 3 years and 7 months (median) in people who had treatment with pembrolizumab. They occurred later in those who received methotrexate.

No differences

In this small study, no difference was found in terms of the following symptoms:

  • Exhaustion
  • Nausea and vomiting
  • Pain
  • Shortness of breath
  • Sleep problems
  • Loss of appetite
  • Constipation
  • Diarrhea
  • Trouble swallowing
  • Abnormal sensations
  • Speech problems
  • Dental problems
  • Trouble opening your mouth
  • Dry mouth
  • Sticky saliva
  • Coughing
  • General feeling of illness

Health-related quality of life: No difference between the treatments was found in terms of various aspects of quality of life either, such as performing daily tasks or problems socializing.

Severe side effects and stopping treatment due to side effects: There was no difference here either.

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 pembrolizumab (Keytruda).