Major trial backs immunotherapy as standard first-line treatment for head and neck cancer

Immunotherapy is better than standard ‘extreme’ chemotherapy as first-line treatment for advanced head and neck cancer and can keep some patients alive for more than three years, a major new trial reports.

24 November 2019

  • Immunotherapy pembrolizumab keeps some patients alive for three years or more
  • Pembrolizumab either used alone or in combination with chemotherapy was more effective than a standard cocktail of chemotherapy drugs in a study involving nearly 900 patients.
  • For patients who responded to treatment, the duration of response was five times longer for pembrolizumab alone than standard ‘extreme’ chemotherapy  
  • Pembrolizumab now approved in Europe as first-line treatment for patients whose tumours express PD-L1 

The immunotherapy drug pembrolizumab alone or in combination with chemotherapy extended patients’ lives compared with standard treatment – with some groups of patients treated with single-agent pembrolizumab responding for five times longer than with standard extreme chemotherapy.

Crucially, the researchers showed it was possible to predict in advance who was more likely to benefit from pembrolizumab by testing for the PD-L1 immune marker in tumours and on surrounding cells – a key step in establishing the drug’s use as a new standard of care.

Pembrolizumab has recently been approved in Europe as first-line treatment for patients diagnosed with advanced head and neck cancer, marking a key milestone in use of immunotherapy as a standard part of cancer treatment.

The phase III trial was led in the UK by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, and involved 882 patients from all over the world who were diagnosed with advanced head and neck cancer.

The research, published in The Lancet, was funded by the treatment’s manufacturer, Merck & Co., Inc., known as MSD outside the US and Canada.

Currently, many patients diagnosed in the UK with advanced head and neck cancer first receive an ‘extreme’ triple combination of two chemotherapies and targeted drug cetuximab. 

Another checkpoint inhibitor immunotherapy called nivolumab is available on the NHS via the Cancer Drugs Fund, but only for patients for whom the chemotherapy combination has failed.

But the new trial found that immunotherapy had even more benefit if it’s used as early as possible in treatment for those who are diagnosed with stage III or IV head and neck cancer, when it has begun to or has spread around the body. 

Around 12,000 people in the UK are diagnosed with head and neck cancer and half will be diagnosed at stage III or IV, so the results could have an impact on a large number of UK patients.

Patients received pembrolizumab combined with chemotherapy, pembrolizumab alone or the extreme combination treatment.

Overall, the response rate was 17 per cent with pembrolizumab alone, 36 per cent with standard chemotherapy and 36 per cent with pembrolizumab plus chemotherapy. 

However, the researchers found that testing for the immune marker PD-L1 in patients’ tumours and surrounding cells could predict who was most likely to respond.

Some 23 per cent of patients who had high levels of PD-L1 in their tumours responded to pembrolizumab alone, and they did so for far longer than chemotherapy – a remarkable average of 23.4 months compared to only 4.5 months in those treated with standard chemotherapy. Even those with moderate levels of PD-L1 responded for 22.6 months.

Many more patients – some 43 per cent – with high levels of PD-L1 responded to immunotherapy plus chemotherapy combination. The average length of response was lower than pembrolizumab alone at 7.1 months, but still 2.6 months longer than standard chemotherapy.  

Pembrolizumab alone had a much lower rate of serious side effects, at 55 per cent, than either extreme chemotherapy or pembrolizumab plus chemotherapy (both 85 per cent).

Study leader Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“In the last five years immunotherapy has had a big impact on the treatment of many cancers, but generally only after standard treatments such as chemotherapy have failed. Our findings are exciting because they show that immunotherapy could have an even greater impact if used earlier, and in many cases spare patients some of the difficult side effects of chemotherapy.

“Pembrolizumab has been approved both as a single agent and with chemotherapy for advanced head and neck cancer by the FDA in the US and by the European Commission. 

“For patients with high levels of the marker PD-L1 whose tumours are smaller and growing relatively slowly, pembrolizumab alone is an excellent treatment option. For patients with larger tumours growing more aggressively, or in those whose tumours express lower levels of the PD-L1 marker, the combination of pembrolizumab and chemotherapy is more likely to be used to get the disease in check.”

This study follows exciting advances in other hard-to-treat cancers, including melanoma. Royal Marsden trials led by Professor James Larkin, whose work is supported by The Royal Marsden Charity, have shown that an immunotherapy combination of drugs called ‘nivolumab’ and ‘ipilimumab’ can have a powerful effect on advanced melanoma. As a result of this research, the drug combination has now become standard practice.

About Head and neck cancers

  • Head and neck cancers are the fastest growing cancers in the UK, currently approaching 12,000 new cases diagnosed each year 
  • The tumour types are diverse and located in around 30 different sites between (but not including) the shoulder blade and the eyes
  • Most cases used to be linked to tobacco and alcohol, but the recent rapid increase in cases seems to be associated with HPV 
  • Other risk factors include: being male, over 40, poor dental hygiene, exposure to inhalents, marijuana use, poor nutrition, weak immune system, and is linked to deprivation
  • Although boys are now also being vaccinated as well as girls, there will be several decades before HPV will cease to be a risk factor
  • Around half of patients are diagnosed at stage III or IV, which is much more difficult to treat, currently requiring chemotherapy, which adds to side effect burden and offers little survival benefit