Researchers have shown for the first time that a drug that prevents cancer cells from repairing can control the growth of mesothelioma, a rare and aggressive form of cancer caused by asbestos.
The results of the NERO clinical trial have been presented at the American Association of Cancer Research conference overnight (Tuesday 29th April).
The findings provide new hope for patients with mesothelioma that has come back after initial treatment and could give people more time with their loved ones.
The NERO trial was run by researchers at the University of Leicester and the Cancer Research Uk Southampton Clinical Trials Unit and was funded by the charity Asthma + Lung UK.
A new hope for patients
Mesothelioma is an aggressive cancer that forms in the lining of the lungs or abdomen and is linked to breathing in or ingesting dangerous asbestos fibres. In the UK around 2,700 people are diagnosed with mesothelioma each year*.
“Currently, only around 5 per cent of people diagnosed with mesothelioma will survive for 5 years or more,” says Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester and co-lead of the NERO trial. “In patients where initial treatment is unsuccessful and the cancer comes back, there are very few further options. Most patients will therefore only receive treatment to control their symptoms, rather than cure the disease.”
The NERO trial looked at a class of drug known as PARP inhibitors which work by blocking the repair of damaged DNA in cancer cells, thereby causing the cancer cells to die.
PARP inhibitors have already been shown to improve the survival of patients with some types of breast and ovarian cancers. A previous study had also shown that mesothelioma does respond to this type of drug, but more evidence was needed as to whether it can improve outcomes for patients.
88 patients whose mesothelioma treatment had stopped working took part in the trial at 11 hospitals across the UK. Those given a PARP inhibitor called niraparib were found to have a 27% reduction in the risk of the cancer progressing or death. This delayed the worsening of mesothelioma by an average of 1.5 months compared to those receiving the standard of care treatments, with a number of patients seeing a much longer period of time where their cancer is being controlled.
“Although this increase may seem small, for this group of patients who have very few treatment options and a generally poor prognosis, this is a significant step forward,” says Professor Gareth Griffiths, Director of the Southampton Clinical Trials Unit and co-lead of the trial. “We have shown for the first time that this kind of drug can improve progression-free survival for mesothelioma patients compared with their usual treatment in the NHS. This gives enormous hope to those patients and their families and means we can now carry out further research to find out more about how these treatments could be tailored and enhanced to stimulate an even better response in more people.”
“I’m so happy to have been part of the trial”
After many years of working on building sites, where asbestos use was commonplace in the 1970s and 80s, architect James Fox was diagnosed with mesothelioma in early 2018.
“I went in to see the oncologist and he looked really glum, and that’s when he gave us the news and I was told I had around six to nine months to live. I was given all these magazines to look at do to with cancer, but I didn’t want to know, I just didn’t want to think about it.”
“I was going into a hospice to have my chemotherapy, and I remember the nurse saying, ‘this is where you’ll be for the last few months of your life’.”
The 83-year-old grandfather of five initially had surgery, chemotherapy and then immunotherapy. But when treatment stopped working, he was invited to join the NERO trial.
“I was told that it was a bit of a lottery to get on to it. But I thought, let’s try it. I mean, what else, I’d gone well past the prognosis by then, so I’d try anything that was offered.”
James’ cancer responded to niraparib so well that when his time on the trial came to an end the drug company agreed to continue supplying the drug so he can continue to benefit from the treatment.
“Obviously, it seems to have worked for me so far. I feel very tired at times, but if I manage it properly, I’m fine.
“The oncologists and oncology nurses have been brilliant; I’ve had fantastic treatment. My wife Bridget has been wonderful giving me support throughout this ordeal over these last seven years. She has cared for me, fed me the recommended food, done most of the driving. I feel this has really contributed to my recovery.”
And with three children and five grandchildren and still working as an architect, James feels he is still able to live life to the full.
“One of the things that’s kept me going is fishing and I’m still able to do that. I used to go to Siberia and get dropped off by helicopter on a little island where the only things were brown bears and salmon. But I can’t do that now, I can’t get insurance. But I still fish locally every week and I go to Scotland a few times a year.”
“I’m so happy to have been part of the trial. It was a marvellous experience and if anyone else is offered the chance to be part of a clinical trial I would advise them to try it.”
Dr Samantha Walker, Director of Research & Innovation at Asthma + Lung UK, said: “Currently, there is no cure for asbestos-related cancer mesothelioma and treatments are limited. The NERO clinical trial, testing a drug with a new mechanism of action, has given people with mesothelioma longer with their loved ones. This trial has made a meaningful difference to people with mesothelioma who were out of treatment options.
“However, clinical trials in the UK are struggling to secure investment, funding for lung health research is on life support. Asthma + Lung UK is working hard to reverse decades-long underinvestment, because lung research breakthroughs can happen and when they do, they save lives. But urgent action is still needed to increase investment into lung research.”
Liz Darlison, CEO of Mesothelioma UK, said: “Mesothelioma UK were delighted to support this study and would like to congratulation the NERO team and thank them on behalf of patients for generating evidence to support a new treatment option. Mesothelioma is a devastating disease, like many rare cancers we are desperate for new treatment options and these findings are a significant step forward, this offers real hope for patients.”
Looking to the future
The NERO team are now looking at the next steps for enhancing treatment for these patients.
“We are already doing some translational analysis on the samples taken from patients on the NERO trial which will tell us whether certain people, with certain genetic biomarkers, may respond even better to the treatment than others,” says Professor Fennell. “We are also looking at an innovative sub-study which will use artificial intelligence to analyse patient scans to look at changes in the amount of cancer present allowing us to spot quickly whether the current treatment is working for the patient, which is a first in this cancer setting.”
Professor Griffiths continues: “We are also looking ahead to our next trial, SELECTmeso, which is a large platform trial testing several different drugs against mesothelioma. This trial will see patients tested for certain biomarkers, or genetic signals, in their tumours and then given the drug that is most likely to work for them. We really hope this step into more personalised medicine could further help these patients who desperately need better treatment options.”
The NERO trial was supported by mesothelioma patient, campaigner and “Meso Warrior” Mavis Nye, who was a long-term collaborator of Professors Fennell and Griffiths and who acted as a patient representative on the trial team as NERO was being set up. Mavis sadly passed away in November 2023 while the trial was taking place.