Pembrolizumab (Keytruda) in combination with chemotherapy for the treatment of advanced, incurable head and neck cancer

In 2020, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether pembrolizumab in combination with platinum-based chemotherapy has any advantages or disadvantages compared to the standard treatment for advanced squamous cell carcinoma of the head and neck – either in adults whose cancer has returned and can’t be operated on, or those whose cancer has spread to other parts of the body (metastasis). In addition, the cancer cells must have the protein PD-L1.

The data on nearly 500 patients in one study was analyzed for this assessment: Half of the participants were given pembrolizumab, and the other half received cetuximab. Both pembrolizumab and cetuximab were combined with platinum-based chemotherapy.

This is what was found:

What are the advantages of pembrolizumab?

Life expectancy: Early results suggest that pembrolizumab in combination with platinum-based chemotherapy can increase life expectancy: People who were given pembrolizumab passed away within nearly 14 months on average (median value), compared to within about 10 months in people who had treatment with cetuximab.

For the severe side effects severe skin diseases and severe immune-mediated side effects, early results suggest that pembrolizumab has an advantage compared to cetuximab. Immune-mediated side effects are diseases in which the immune system attacks your own body.

The study also suggests that pembrolizumab has an advantage in terms of skin infections along the nails (paronychia): These infections only affected people who were given cetuximab (about 12 out of 100).

What are the disadvantages of pembrolizumab?

Pain: Early results suggest that pembrolizumab in combination with chemotherapy has disadvantages compared to cetuximab in people whose cancer has spread to other parts of the body: In this study, about 31 out of 100 people who used pembrolizumab experienced the typical cancer-related pain, compared to about 18 out of 100 people who were given cetuximab. There was no difference between the treatment groups for people whose cancer had returned, though.

Exhaustion: Early results suggest that pembrolizumab has disadvantages here in women: About 46 out of 100 women who were given pembrolizumab felt exhausted, compared to only about 27 out of 100 women who received cetuximab.

Feeling ill: Early results suggest that pembrolizumab also has disadvantages here in women: About 33 out of 100 women who were given pembrolizumab felt ill, compared to only about 10 out of 100 women who received cetuximab.

The early results suggest that pembrolizumab has a disadvantage in terms of specific severe side effects:

  • Severe anemia: About 24 out of 100 people who were given pembrolizumab experienced this severe side effect, compared to about 15 out of 100 people who used cetuximab.
  • Severe inflammation of the mucous membranes: About 11 out of 100 people who were given pembrolizumab experienced severe side effects in the mucous membranes, compared to about 5 out of 100 people who had the standard treatment. About 8 out of 100 people who were given pembrolizumab experienced severe inflammations in the mucous membranes lining the mouth (stomatitis), compared to about 4 out of 100 people who used cetuximab.
  • Severe problems affecting the airways: About 15 out of 100 people in the study who were given pembrolizumab experienced severe respiratory side effects, compared to about 7 out of 100 people who received cetuximab.

Health-related quality of life:

  • Cognitive functioning: Early results suggest that women who had treatment with pembrolizumab and chemotherapy had more trouble concentrating and remembering things: About 40 out of 100 women who were given pembrolizumab had these problems, compared to only about 17 out of 100 women who received cetuximab. There was no difference in men.
  • Physical functioning: Early results suggest that people under the age of 65 who had treatment with pembrolizumab and chemotherapy had more trouble managing the physical activities of everyday life, such as shopping, eating or washing themselves. About 34 out of 100 people under the age of 65 who were given pembrolizumab had these problems, compared to only about 22 out of 100 people in the same age group who had treatment with cetuximab. There was no difference in older people.
  • Eating in public: Based on the early results, people under the age of 65 who had treatment with pembrolizumab and chemotherapy also had more trouble eating in public than people who were given cetuximab did. About 26 out of 100 people in this study under the age of 65 who were given pembrolizumab had these problems, compared to only about 16 out of 100 people in the same age group who had the standard treatment. There was no difference here in older people.

No difference

Overall health: The patients in the study were asked how they would rate their health. There was no difference here between the treatment groups.

Cancer symptoms: There was also no (relevant) difference in terms of various cancer symptoms, including:

  • Nausea and vomiting
  • Shortness of breath (dyspnea)
  • Loss of appetite
  • Constipation
  • Diarrhea
  • Trouble swallowing
  • Dry mouth
  • Problems sleeping

Health-related quality of life: There was no difference between the treatments in terms of things like being together with other people (social contact), sexuality, and how patients rate their overall health and quality of life.

Overall severe side effects and treatment stopped due to side effects: There was no difference between the treatments here. Overall, about 85 out of 100 people had severe side effects, regardless of which treatment they had. About 30 out of 100 people stopped their treatment due to the side effects.