Immunotherapy improves survival for people with aggressive, asbestos-linked lung cancer

People with an aggressive form of lung cancer that’s come back after treatment, leaving them with limited options, could live longer when treated with an immunotherapy currently available for several types of cancer.

The trial, funded by Cancer Research UK’s Stand Up To Cancer campaign, found that the immunotherapy drug nivolumab increased survival and made the disease more stable for patients with relapsed mesothelioma when compared to those in the placebo group.
This is the first study to show that a treatment has been able to improve survival in patients with mesothelioma that’s come back after chemotherapy. The findings were presented at the World Conference on Lung Cancer today.

A ‘game-changer’

Mesothelioma develops in the lining of the lungs or abdomen, with most cases caused by exposure to the now outlawed industrial material, asbestos.

“Asbestos might seem like a threat of the past, but for many, it’s left quite literal scars that are only being seen now. Mesothelioma is a relatively rare disease, but it is a devastating one. We wanted to do anything we could to find better treatments for these patients, despite being in the midst of a global pandemic,” said Professor Dean Fennell, director of the Leicester Mesothelioma Research Programme, co-lead on the study.

Cases of mesothelioma in the UK have increased by 61% since the early 1990s. Cases are particularly high in areas of the UK where shipping and mining industries formerly thrived. And in England, only 7% of people diagnosed with mesothelioma survive their disease for 5 years or more.

People with mesothelioma are usually treated with chemotherapy, surgery or radiotherapy. But options start to become limited once people stop responding to their treatment. Something the team were keen to change.

The CONFIRM trial involved 332 people with mesothelioma from across the UK whose tumours were still growing despite being treated with standard chemotherapy and could not be removed with surgery. Two thirds were randomised to take nivolumab once every fortnight, with the rest receiving a dummy drug.

People taking nivolumab lived on average for 9.2 months, compared to 6.6 months for those in the placebo group.

Patients who received nivolumab also had more stable disease. The risk of their cancer progressing was reduced by 39%, with people not seeing their cancer worsening for 3.0 months compared with 1.8 months in the placebo group.

“This trial shows clear evidence of benefit and marks a major breakthrough in the treatment of mesothelioma, a disease where there are currently very few options for patients when first-line chemotherapy has stopped working and prognosis is often very poor,” said Professor Gareth Griffiths, director of the Cancer Research UK Southampton Clinical Trials Unit at the University of Southampton.

Griffiths, who led the study with Fennell, added that it’s the first study ever to show improved survival and we therefore believe that nivolumab could be a game-changer for treating mesothelioma patients in the future.”

Liz Darlison, CEO at Mesothelioma UK said the charity was delighted to support the study by covering patient travel. Between April 2018 and October 2020, Meso UK awarded £24,507.99 in travel grants to patients taking part in the CONFIRM trial. Liz added: “We’re focused on equitable access to clinical trials so the CONFIRM trial team is to be congratulated on having so many sites open, so well distributed across the country. These results have the potential to provide a long overdue new treatment option and a huge dose of hope. We thank all involved, especially the patients that took part.”

“I jumped at the chance to join the trial”

Carol Wesson, 73, from Wimborne in Dorset, was one of the people who took part in the CONFIRM trial. Carol developed mesothelioma after years working for a company that used asbestos rope as a door seal in the manufacture of stoves.

“I didn’t work on the factory floor,” says Carol. “I was in the sales team and worked mainly in the office. But sometimes when things were busy, or a customer needed a replacement seal, I would help out by going into the factory and cutting a piece of the asbestos rope. I just used a pair of big scissors and you could see the fibres coming off the rope as I cut.”
In late 2016, Carol began to notice changes to how she was feeling. “I would be out walking my dogs and I would start to feel breathless going up hills.” Carol developed a cough in the New Year and was referred to hospital, where she was diagnose with cancer.

“The day I was diagnosed I was told the prognosis was about a year. I was completely shocked, stunned. There was no cancer in my family, just heart disease. I had never been ill in my life. I had worked for years without a day’s sickness.”

Carol was treated with chemotherapy. But she was then given the chance to take part in an early-phase clinical trial called VIM, and later went on to participate in CONFIRM.

“I think it is so important for patients to be involved in research. When I was offered the chance to be part of the CONFIRM trial at Bournemouth Hospital, I jumped at it. It’s wonderful knowing that you are not only potentially helping yourself, but also helping improve treatment for more patients in the future.”

Carol Wesson is one of the patients who has been able to receive nivolumab through the NHS 8 months after she finished on the CONFIRM trial. And it’s made a huge difference.
“I can go out and walk my dogs, I split logs for my wood burner, and I do my garden. I can’t do everything exactly as I used to but then I am 73. I don’t take much notice of my age any more than I do of my tumour. I just get on with enjoying my life.”

A long overdue new option

Nivolumab is already approved to treat some people with advanced kidney and non small lung cancers in the UK, as well as some advanced melanomas.

During the COVID-19 pandemic, NHS England endorsed nivolumab for some people with malignant mesothelioma as an alternative to chemotherapy, because it has less of a suppressive effect on the immune system and could reduce the risk of someone becoming seriously ill during the pandemic. This decision is currently in place until the end of March, but the data from the CONFIRM trial could help to make this option permanently available to patients.

Michelle Mitchell, Cancer Research UK’s chief executive, said that 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.”