New hope for patients with aggressive asbestos-linked cancer
Researchers have shown a targeted drug treatment can control the growth of a rare form of cancer caused by asbestos.
Mesothelioma is a rare and aggressive type of cancer. The NERO trial showed targeted treatment with a drug that prevents cancer cells from repairing can improve survival.
The results have been presented at the American Association of Cancer Research conference. They provide new hope for patients with mesothelioma that has come back after initial treatment.
The trial was run by researchers at the University of Leicester and the Cancer Research UK Southampton Clinical Trials Unit. It was funded by the charity Asthma + Lung UK.
University Hospital Southampton (UHS) was the trial sponsor.
A new hope for patients
Mesothelioma is an aggressive cancer that forms in the lining of the lungs or abdomen. It is linked to breathing in or ingesting dangerous asbestos fibres.
“Currently, only around five percent of people diagnosed with mesothelioma will survive for five 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. These work by blocking the repair of damaged DNA in cancer cells, 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 mesothelioma responds to this type of drug. However, more evidence was needed as to whether it could improve outcomes for patients.
88 patients whose mesothelioma treatment had stopped working took part in the trial at 11 hospitals across the UK, including UHS.
Dr Judith Cave, Medical Oncology Consultant, led UHS’ involvement in the trial. She is also Associate Director of Medical Education, and part of the UHS Research Leaders Programme.
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. Some patients had a much longer period of time where their cancer was 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. He can therefore 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.”
With three children, five grandchildren and his work 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. I can’t do that now, as 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.”
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. This 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 says: “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.