Drug offers ‘wonderful’ breakthrough in treatment of asbestos-linked cancer
Scientists have developed a drug to treat mesothelioma, a notoriously hardto-treat cancer linked to asbestos, in the biggest breakthrough in two decades.
Thousands of people are diagnosed with the disease globally every year, which tends to develop in the lungs and is mainly caused by exposure to asbestos at work. It is aggressive and deadly, and has one of the world’s worst cancer survival rates.
Now scientists are hailing the “truly wonderful” arrival of a new therapy, which they say should offer fresh hope to those with the disease and their families.
In an international trial spanning five countries, led by Queen Mary University of London, a new drug that cuts off the tumour’s food supply quadrupled three-year survival rates. The results were published in the journal JAMA Oncology.
“This trial has changed the lives of people with mesothelioma, allowing us to live longer,” said one of the patients who benefited from the drug. The 80year-old, who wished to remain anonymous, won compensation from his former employer after being exposed to asbestos in a factory in the 1970s.
He was given four months to live, but thanks to the trial is still alive five years later. “I have five grandchildren and two great-grandchildren now – I wouldn’t want to miss all that,” he said.
The breakthrough is significant, experts say, because mesothelioma has one of the lowest survival rates of any cancer. The new drug, ADI-PEG20 (pegargiminase), is the first of its kind to be successfully combined with chemotherapy in 20 years.
The trial involved patients from the UK, US, Australia, Italy and Taiwan, and was led by Prof Peter Szlosarek at Queen Mary. Each received chemotherapy every three weeks for up to six cycles. Half were also given injections of new drug, while the other half received a placebo for two years.
Among the patients included in the final analysis were 249 people with pleural mesothelioma – when the disease affects the lining of the lungs.
They had an average age of 70.
The study, known as the ATOMICmeso trial, was conducted at 43 centres in the five countries between 2017 and 2021. Those who received pegargiminase and chemotherapy survived for an average of 9.3 months, compared with 7.7 months for those who had the placebo and chemotherapy, according to the results published in JAMA Oncology.
The average “progression-free survival” was 6.2 months with pegargiminase-chemotherapy, compared with 5.6 months among patients who had the placebo and chemotherapy.
“In this pivotal, randomised, placebo-controlled, phase 3 trial in 249 patients with pleural mesothelioma, pegargiminase-chemotherapy increased significantly the median overall survival by 1.6 months and quadrupled the survival at 36 months compared to placebo-chemotherapy,” the authors wrote.
“Pegargiminase-based chemotherapy was well tolerated with no new safety signals.”
The breakthrough follows two decades of work by Szlosarek, after his original discovery that mesothelioma cells lack a protein called ASS1, which enables cells to manufacture the amino acid arginine.
This knowledge was used to develop the drug. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that cannot manufacture their own arginine, this means their growth is thwarted.
“It’s truly wonderful to see the research into the arginine starvation of cancer cells come to fruition,” said Szlosarek.
“This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma.”
Dr Tayyaba Jiwani of Cancer Research UK, which funded the research alongside the biotechnology company Polaris Group, said: “This study shows the power of discovery research which allows us to dig deep into the biology of mesothelioma to uncover vulnerabilities that we can now target with ADI-PEG20.”
Liz Darlison, chief executive of the charity Mesothelioma UK, said: “The UK mesothelioma community, including doctors, nurses, patients and families living with mesothelioma, are extremely proud of ATOMIC. It offers another much-needed treatment option and, above all, hope to those living with mesothelioma.
“We look forward to seeing this treatment become available as a standard option to all patients in the future.”