New treatment for a rare and aggressive cancer improves survival rates in breakthrough clinical trial

A phase 3 clinical trial, led by Professor Peter Slussark at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), which has limited treatment options. Colon is a rare and often rapidly fatal form of cancer.

Mick’s journey with mesothelioma: “I have five grandchildren and two great-grandchildren — I wouldn’t want to miss them all.”

The ATOMIC-meso trial, a randomized placebo-controlled study of 249 patients with MPM, found that one treatment — combining a new drug ADI-PEG20 with conventional chemotherapy — extended participants’ median survival by 1.6 months. increased, and quadrupled survival at 36 months compared with placebo chemotherapy.

The findings are important, as MPM has the lowest 5-year survival rate of any solid cancer of 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets a cancer’s metabolism developed for this disease in 20 years.

MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with asbestos exposure. It is usually treated with powerful chemotherapy drugs, but these are rarely able to stop the disease from progressing.

The premise behind this new drug treatment is beautiful in its simplicity — starving the tumor by cutting off its food supply. All cells need nutrients to grow and develop, including amino acids such as arginine. ADI-PEG20 works by reducing blood arginine levels. For tumor cells that cannot make their own arginine because the enzyme is missing, this means that their growth is stunted.

The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute, which began with Professor Slussark’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables the cells to make their own arginine. makes He and his team have since devoted their efforts to using this knowledge to develop an effective treatment for MPM patients.

Professor Szlosarek said: “It’s really amazing to see the research on arginine starvation of cancer cells coming to fruition. This discovery is something I’ve been driving since my early stages in the lab, with a new treatment ADI-PEG20. Now things are getting better. Patients’ lives are affected by mesothelioma. I thank all the patients and families, the investigators and their teams, and Polaris Pharmaceuticals for their commitment to developing new cancer treatments.”

Dr Tayyaba Jiwani, Science Engagement Manager at Cancer Research UK, said: “This study shows the power of discovery research which allows us to dig deeper into the biology of mesothelioma so that we can uncover the risks we face. Can now target with ADI-PEG20.

“Cancer Research UK is delighted to be funding the early stages of this research, including an early clinical trial which proved the safety and effectiveness of this drug.”

Studies evaluating ADI-PEG20 in patients with sarcoma or glioblastoma multiforme (a type of brain tumor) and other arginine-dependent cancers are ongoing. The success of this novel chemotherapy in MPM also suggests that the drug may be beneficial in the treatment of several other types of cancer.

Mick’s journey with mesothelioma

Mick worked in the boiler room of a factory in the 1970s, where he was exposed to asbestos. In 2018, he went to his doctor when he started feeling unwell and lost three stone in weight. He became anemic and was eventually diagnosed with mesothelioma.

“It was a bit of a shock: I was given four months to live,” Mac explains. Her doctor referred her to Professor Slussark, who enrolled her in the ATOMIC-meso trial. “I always believed in Peter. I said: ‘I’m here to win it – you’re not getting rid of me.’ And here I am five years later.”

For two years, Mike visited St. Bartholomew’s Hospital every week, accompanied by his wife, Jackie, or one of his children or grandchildren. “I would get two injections of the new treatment — one in each arm. I had no serious side effects,” Mick explains. “I met a lot of other people during the trial. Over time, some of them disappeared. But I kept going.”

Mike was awarded compensation from his former employer who was responsible for the asbestos exposure that ultimately led to his mesothelioma. About 80 percent of mesothelioma cases are caused by workplace exposure.

Two and a half years after Mick enrolled in the ATOMIC-meso trial, his mesothelioma returned and he received a second course of treatment, this time immunotherapy. He experienced more side effects with this therapy, including encephalitis. But his cancer is still under control, and he was able to celebrate his 80th birthday recently. Professor Szlosarek and his team plan to study why some patients, like Mick, benefit so much from ADI-PEG20, in the hope of spreading this benefit to more people.

Mike says: “This trial has changed the lives of people with mesothelioma, allowing us to live longer. I now have five grandchildren and two great-grandchildren — I don’t want to miss them all. “