Groundbreaking treatment quadruples survival rate for people with aggressive cancers
Treatment has quadrupled survival rates at 36 months compared to those receiving placebo-chemotherapy. (CREDIT: Creative Commons)
In a groundbreaking advancement in cancer treatment, a phase 3 clinical trial led by Professor Peter Szlosarek at Queen Mary University of London and sponsored by Polaris Pharmaceuticals has revealed promising results in tackling malignant pleural mesothelioma (MPM), a rare and often swiftly fatal form of cancer with limited therapeutic options.
The ATOMIC-meso trial, a randomized placebo-controlled study, published in JAMA Oncology, involving 249 patients with MPM, has demonstrated that a combination treatment, merging a novel drug named ADI-PEG20 with traditional chemotherapy, has extended the median survival of participants by 1.6 months. Additionally, it has quadrupled survival rates at 36 months compared to those receiving placebo-chemotherapy.
"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," expressed Professor Szlosarek, reflecting on the research's progression. "I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy."
Dr. Tayyaba Jiwani, Science Engagement Manager at Cancer Research UK, emphasized the significance of such research endeavors: "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."
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MPM, a rare and aggressive cancer affecting the lining of the lungs, typically stems from exposure to asbestos. Conventional treatments predominantly involve potent chemotherapy drugs, but their efficacy in halting disease progression remains limited.
The essence of this innovative drug treatment lies in its simplicity – starving the tumor by cutting off its nutrient supply. ADI-PEG20 operates by depleting arginine levels in the bloodstream, essential for cell growth and multiplication. This deprivation particularly impacts tumor cells incapable of manufacturing their arginine due to a missing enzyme, effectively hindering their proliferation.
The roots of the ATOMIC-meso trial trace back to two decades of research at Queen Mary’s Barts Cancer Institute, initiated by Professor Szlosarek's discovery that malignant mesothelioma cells lack a crucial protein called ASS1, vital for arginine synthesis.
Leveraging this insight, the team dedicated efforts to develop an effective treatment strategy for MPM patients.
Mick’s Journey with Mesothelioma
Mick, a former worker in a factory boiler room in the 1970s, experienced asbestos exposure during his tenure. His encounter with mesothelioma began in 2018 when he noticed alarming health declines, prompting a visit to his doctor, who diagnosed him with the disease.
Overall and Progression-Free Survival in Phase 3 Patients (Intention-to-Treat Population). Analysis population was the intention-to-treat population, which included all randomized patients. A, Overall survival (OS) was calculated as the time from randomization until death. (CREDIT: JAMA Network)
“It was a bit of a shock: I was given four months to live,” recalls Mick. Referral to Professor Szlosarek led to his enrollment in the ATOMIC-meso trial. Determined, Mick stated, “I always believed in Peter. I said: ‘I’m in it to win it – you’re not getting rid of me.’ And here I am five years later.”
For two years, Mick underwent weekly treatments at St Bartholomew’s Hospital, receiving two injections of the new treatment during each visit, with minimal side effects. Interactions with fellow trial participants revealed the harsh reality of the disease, as some gradually succumbed to its effects over time.
Mick's experience epitomizes the occupational hazard associated with mesothelioma, as around 80% of cases are linked to workplace exposure, leading to legal recourse for affected individuals.
Following a recurrence of his mesothelioma, Mick embarked on a second course of treatment, this time opting for immunotherapy. Despite encountering more side effects, including encephalitis, his cancer remains under control, allowing him to celebrate his 80th birthday.
Reflecting on his journey, Mick acknowledges the transformative impact of the trial, extending the lives of those afflicted by mesothelioma. “This trial has changed the lives of people with mesothelioma, allowing us to live longer," he says. "I have five grandchildren and two great-grandchildren now – I wouldn’t want to miss all that.”
Overall and Progression-Free Survival in Phase 3 Patients (Intention-to-Treat Population). Progression-free survival (PFS) was calculated as the time from randomization until date of tumor progression or death. (CREDIT: JAMA Network)
The success of the ATOMIC-meso trial not only represents a milestone in MPM treatment but also holds promise for addressing other cancers reliant on arginine metabolism. Ongoing studies exploring ADI-PEG20's efficacy in sarcoma, glioblastoma multiforme, and various other cancers underscore its potential as a versatile therapeutic agent.
Looking ahead, Professor Szlosarek and his team are committed to unraveling the underlying mechanisms behind patients' varied responses to ADI-PEG20, aiming to broaden its benefits to a larger demographic. Through relentless dedication and collaborative efforts, this breakthrough offers renewed hope for individuals battling mesothelioma and beyond.
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