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

Space-filling model of immunotherapy pembrolizumab

Image: Space-filling model of immunotherapy pembrolizumab

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.

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 Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and involved 882 patients from all over the world who were diagnosed with advanced head and neck cancer.

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

'Impact on a large number of UK patients'

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. 

Testing for PD-L1

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).

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'Greater impact if used earlier'

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.”

'A test for picking out who is most likely to benefit'

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“We have seen a series of innovative new cancer treatments coming through over the last few years, but the next big challenge is to get them to patients as early as possible in the treatment pathway, as this new research does.

“This study is very exciting for two reasons – firstly because it shows that immunotherapy can have dramatic benefits for some patients with head and neck cancer when used as a first-line treatment, and secondly because the researchers have devised a test for picking out who is most likely to benefit.

“At the ICR, we want to see every new drug that comes on the market accompanied by a test to target its use as precisely as possible. That will make sure we don’t subject patients to treatments that were never likely to work for them, and should make new precision medicines more affordable for the NHS too.”


Kevin Harrington Paul Workman immunotherapy head and neck cancer pembrolizumab research highlight
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