ADI-PEG20 (Pegargiminase-Chemotherapy) for Nonepithelioid Pleural Mesothelioma

ADI-PEG20, a novel therapeutic approach is providing new hope to patients with Nonepithelioid Pleural Mesothelioma. Recent results from a clinical trial, published in JAMA Oncology in February 2024, indicate that combining chemotherapy with ADI-PEG20 significantly improves patient outcomes.

Clinical Trial Overview

The clinical trial, conducted from 2017 to 2021 across 43 centers in five countries (UK, US, Australia, Italy, and Taiwan), demonstrated that the combination of ADI-PEG20 and chemotherapy extends overall survival by 1.6 months and increases the 36-month survival rate fourfold compared to the placebo-chemotherapy group. The study included a 12-month follow-up period to monitor long-term effects and patient progress.

About Pleural Mesothelioma

Pleural mesothelioma, a malignant cancer affecting the lining of the lungs, has one of the lowest 5-year survival rates among solid cancers, ranging from 5% to 10%. This aggressive cancer is predominantly caused by workplace asbestos exposure and presents significant treatment challenges.

Mechanism of ADI-PEG20

The pivotal discovery underlying this treatment is that mesothelioma cells lack argininosuccinate synthetase 1 (ASS1), a protein necessary for synthesizing the amino acid arginine. Without ASS1, cancer cells cannot produce arginine, making them susceptible to growth inhibition through arginine deprivation. ADI-PEG20 exploits this vulnerability by depleting arginine levels in the bloodstream, effectively starving the tumor cells and impeding their growth.

Implications and Future Research

The findings from this study suggest that ADI-PEG20, in conjunction with chemotherapy, holds significant promise for improving survival outcomes in pleural mesothelioma patients. However, ongoing research is essential to further understand the biological mechanisms of mesothelioma and to explore additional therapeutic strategies. The integration of amino acid deprivation approaches, such as ADI-PEG20, represents a promising advancement in the treatment landscape for this challenging cancer.