Scientists in the UK have developed a new drug that offers a breakthrough treatment for mesothelioma, a deadly cancer caused by asbestos exposure. The drug, called pegargiminase, works by starving the tumour cells of a vital nutrient, arginine, and enhancing the effects of chemotherapy. The drug has shown promising results in a large international trial, increasing the survival rates and quality of life of patients with this aggressive disease.
What is mesothelioma?
Mesothelioma is a type of cancer that affects the lining of the lungs, chest or abdomen. It is mainly caused by inhaling asbestos fibres, which can damage the DNA of the cells and cause them to grow out of control. Asbestos is a mineral that was widely used in construction, insulation and other industries until the 1980s, when its health risks became known. However, mesothelioma can take decades to develop after exposure, so many people are still diagnosed with the disease today.
Mesothelioma is one of the most difficult cancers to treat, as it often does not cause any symptoms until it is advanced and has spread to other organs. The average survival time after diagnosis is only about 12 months, and there is no cure for the disease. The standard treatment is chemotherapy, which can slow down the growth of the tumour and relieve some symptoms, but has many side effects and does not work for everyone.
How does pegargiminase work?
Pegargiminase is a new drug that targets a specific feature of mesothelioma cells: their dependence on arginine. Arginine is an amino acid that is essential for many biological processes, such as protein synthesis, cell division and wound healing. Most cells can produce their own arginine from other sources, but mesothelioma cells have lost this ability and rely on getting it from the bloodstream.
Pegargiminase works by depleting arginine levels in the blood, starving the mesothelioma cells and preventing them from growing and spreading. At the same time, pegargiminase enhances the effects of chemotherapy by making the cancer cells more sensitive to the drugs. Pegargiminase is given as an injection every week, along with chemotherapy every three weeks.
What are the results of the trial?
The trial of pegargiminase was conducted by researchers from Queen Mary University of London and other institutions in five countries: the UK, the US, Australia, Italy and Taiwan. The trial involved 249 patients with pleural mesothelioma (affecting the lining of the lungs), who were randomly assigned to receive either pegargiminase plus chemotherapy or placebo plus chemotherapy.
The results of the trial were published in JAMA Oncology and showed that pegargiminase improved both the overall survival and the progression-free survival of patients with mesothelioma. The overall survival is the time from randomisation until death from any cause, while the progression-free survival is the time from randomisation until the tumour grows or spreads.
The average overall survival was 9.3 months for patients who received pegargiminase plus chemotherapy, compared to 7.7 months for those who received placebo plus chemotherapy. This means that pegargiminase extended the average survival by 1.6 months, or 21%. The average progression-free survival was 6.2 months for patients who received pegargiminase plus chemotherapy, compared to 5.6 months for those who received placebo plus chemotherapy. This means that pegargiminase delayed the average progression by 0.6 months, or 11%.
Moreover, pegargiminase increased the chances of surviving for longer periods of time. For example, 15% of patients who received pegargiminase plus chemotherapy were alive at 24 months after randomisation, compared to 8% of those who received placebo plus chemotherapy. At 36 months after randomisation, 4% of patients who received pegargiminase plus chemotherapy were alive, compared to only 1% of those who received placebo plus chemotherapy. This means that pegargiminase quadrupled the three-year survival rate.
The researchers also reported that pegargiminase was well tolerated by most patients and did not cause any new or unexpected side effects. The most common side effects were fatigue, nausea and vomiting, which were similar in both groups.
What are the implications of this study?
This study is a major breakthrough in the treatment of mesothelioma, as it shows that pegargiminase can improve both the quantity and quality of life of patients with this incurable disease. Pegargiminase is the first new drug to be successfully combined with chemotherapy for mesothelioma in 20 years, and the first drug to target the metabolism of the cancer cells. The researchers hope that pegargiminase will soon be approved by the regulatory authorities and become available for patients who need it.
The study also opens up new avenues for research, as pegargiminase may be effective for other types of cancer that depend on arginine, such as melanoma, prostate cancer and liver cancer. The researchers are planning to conduct further trials to test pegargiminase in different settings and combinations, and to explore its mechanisms of action and resistance.
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