Scientists have developed a drug to treat mesothelioma, a notoriously hard-to-treat cancer linked to asbestos, in the biggest breakthrough in two decades.
Thousands of people worldwide are diagnosed with the disease every year, which tends to develop in the lungs and 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 new 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 crop’s food supply quadrupled the three-year survival rate. The results were published in the journal JAMA Oncology.
“This trial changed the lives of people with mesothelioma, enabling us to live longer,” said one of the patients who benefited from the drug. The 80-year-old, who wished to remain anonymous, won compensation from his former employer after he was 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 now have five grandchildren and two great-grandchildren – I wouldn’t want to miss it all,” 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, USA, Australia, Italy and Taiwan, and was led by Prof Peter Szlosarek at Queen Mary. Each received up to six cycles of chemotherapy every three weeks. Half were also given injections of the new medicine, 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 ATOMIC meso-trial, was carried out between 2017 and 2021 at 43 centers in the five countries. Those who received pegargiminase and chemotherapy survived an average of 9.3 months, compared with 7.7 months for those who received 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, randomized, placebo-controlled, phase 3 trial in 249 patients with pleural mesothelioma, pegargiminase chemotherapy significantly increased median overall survival by 1.6 months and quadrupled survival at 36 months compared with 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, following his original discovery that mesothelioma cells have a protein called ASS1, which enables cells to produce the amino acid arginine.
This knowledge was used to develop the drug. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumor cells that cannot produce their own arginine, this means that their growth is stunted.
“It is truly wonderful to see the research on arginine starvation of cancer cells come to fruition,” said Szlosarek. “This discovery is something that I have driven from the earliest stages in the lab, with a new treatment, ADI-PEG20, that is now improving patient lives affected by mesothelioma.”
Dr. Tayyaba Jiwani from Cancer Research UK, which co-funded the research with biotech company Polaris Group, said: “This study demonstrates the power of discovery research which allows us to dig deep into the biology of mesothelioma to uncover vulnerabilities that we now have with ADI- PEG20 can target.”
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, most importantly, hope to those living with mesothelioma.
“We look forward to seeing this treatment become available as a standard option for all patients in the future.”
