Breakthrough results for the treatment of mesothelioma published in The Lancet

The results of the first ever trial of its kind to show improved survival for people with mesothelioma have been published in The Lancet.

The CONFIRM ¹ trial was led by Professor Dean Fennell (right) at the University of Leicester and Professor Gareth Griffiths (left) at the CRUK Southampton Clinical Trials Unit ² , based at the University of Southampton’s Centre for Cancer Immunology.

The findings mean people diagnosed with the aggressive form of cancer, linked to breathing in asbestos fibres, could have more time with their loved ones when prescribed an immunotherapy drug currently used to treat several other types of cancer.

Mesothelioma is traditionally treated with surgery, chemotherapy and radiotherapy. Until now, there have been few options available when patients no longer respond to treatment.

However, the CONFIRM trial, which is funded by Cancer Research UK’s Stand Up To Cancer ³ campaign, looked at whether the immunotherapy drug nivolumab could prolong her life by boosting the body’s immune system to recognise and kill cancer cells.

332 patients with mesothelioma in either the lung or the abdomen were involved in the randomised Phase III study. 111 patients received a placebo and 221 were given nivolumab in the hope of extending their life expectancies.

The trial showed a 33% reduction in the risk of their condition worsening and a 31% reduction in the risk of them dying if they had been treated with the immunotherapy drug. This was equivalent to an additional 3-4 months of life.

The CONFIRM trial is the first of its kind to show that a treatment has improved survival in patients whose mesothelioma has returned after chemotherapy. The preliminary results of the trial were presented at the World Conference on Lung Cancer in January when it became clear that the trial has shown clear evidence of benefit mesothelioma patients, and today (15th October) the full results have been published in The Lancet Oncology.

Professor Gareth Griffiths, director of the Southampton Clinical Trials Unit and co-chief investigator of CONFIRM, said: “This is a significant breakthrough because mesothelioma is a pretty nasty cancer and the treatment options have been very limited.

“Many other cancers have lots of different lines of treatments. Patients may try the first line of treatment and if that doesn’t work, they may try the second and third and even fourth. Now, what we’ve found with mesothelioma is, that if their first chemo doesn’t work, we have now found clear evidence that giving immunotherapy as a second or third line of treatment is of benefit to our mesothelioma patients.

“It’s a fantastic result and we hope that this could become the new standard of care for our future mesothelioma patients in the NHS.”

Nivolumab works by blocking a protein (PD-1) which stops our own immune system attacking the mesothelioma. While chemotherapy uses drugs to kill the cancer cells, the immunotherapy drug effectively shines a torch on the cancer cells, to enable the patient’s own immune system to kill them instead.

Professor Dean Fennell, co-Chief Investigator of the trial, said: “Malignant mesothelioma is a rare disease and there is a huge need for more effective treatments. This is the first study ever to show increased survival for relapsed mesothelioma. The trial involved patients at any stage of disease relapse, and this study therefore shows that immunotherapy can be effective treatment at all disease stages.

We also worked very closely with our partners at Mesothelioma UK and PPI leads representing their ‘mesowarrior community’ which made a real impact in opening and recruiting participants into this trial ahead of target”

In addition to documenting the promising results, the CONFIRM team have also collected the costs involved in treating patients with nivolumab so that the National Institute for Clinical Excellence (NICE) can consider the costs to the NHS in using this treatment against the benefits observed in the CONFIRM trial.

It is hoped the drug will be approved for use on the NHS for future mesothelioma patients based on the results of the study and the fact it has already been used on the NHS as a temporary alternative to chemotherapy for mesothelioma patients during the COVID-19 pandemic.

The team is also working to analyse the samples collected within the trial to further understand the mechanisms by which the immunotherapy treatment works in mesothelioma and which patients benefit. It is hoped this will lead to new trials ideas which will look to make further advances in the treatment options of our mesothelioma patients.

“Immunotherapy drug trial has kept me alive”

Carol Wesson was given just a year to live when she was diagnosed with mesothelioma in 2017 as a result of being exposed to asbestos at work.

Due to her poor prognosis, the 73-year-old was offered the chance to be part of the CONFIRM trial in the hope it could buy her more time.

“I’d never been ill in my life,” said Carol. “But when I was walking my dogs, I noticed I was getting breathless. When I was told I had cancer and found out I only had a year to live, I thought, ‘I had better go off and do as much as I can do.’”

“When I signed up for the trial, I knew there was a chance I could benefit but I also knew I may have been given a placebo. Either way, I wanted to do it to help other people.

“During the trial, the nurse said to me, ‘There’s something about you Carol, your results are incredible.’ The tumour had reduced down to a very small amount and now I am about 90% back to normal. It completely changed my life. It’s kept me alive!”

Carol is backing Stand Up To Cancer, the joint national fundraising campaign from Cancer Research UK and Channel 4, that brings the UK together to speed up progress in life-saving cancer research.

Around 90 people are diagnosed with mesothelioma in Hampshire each year ⁴ and most cases are caused by exposure to asbestos. It can develop in the lining of the lung (the pleura) from inhalation, as well as the peritoneum (the tissue that lines the abdominal wall) after unintentionally ingesting the fibres. Rates are often higher in areas where shipping and mining industries were once popular.

The material is now outlawed but cases of mesothelioma have increased since the early 1990s.

Four years after her diagnosis, Carol is making the most of the extra time she has been given and is enjoying life without the breathlessness that first led to her diagnosis.

She said, “I’m enjoying walking my dogs again and living normally. A time will come when I have to take it all seriously but why do that now when I don’t have to?”

Michelle Mitchell, Cancer Research UK’s chief executive, said: “Nearly half a century ago, Cancer Research UK scientists added to the understanding of just how dangerous asbestos could be. This research helped change regulations, reducing workers exposure to this deadly substance. But mesothelioma can take over 40 years to develop, and the long and painful legacy of asbestos use is still sadly being felt today.

"It’s wonderful news to hear that we may have found a new treatment for people with mesothelioma who have run out of options, when there has been so little progress over the years. We hope that NICE considers nivolumab as a treatment option, which will give people with mesothelioma precious extra time with their loved ones.”

Researchers at the CRUK Southampton Clinical Trials Unit are now hoping a similar immunotherapy drug could provide more time for patients with bladder cancer and are seeking volunteers to take part in a new trial called BL-13. The study aims to establish if the immunotherapy drug Durvalumab can boost the immune system in people with muscle-invasive bladder cancer (where the cancer has spread to the lining of the bladder) that have opted for radiotherapy treatment. It’s hoped the immunotherapy will enable the body to fight the cancer and reduce the chances of the disease returning.

Read more about BL-13 here .