Pegylated arginine deiminase (ADI-PEG20) improved progression-free survival, in contrast with best supportive care, among patients with argininosuccinate synthetase 1 (ASS1)-deficient malignant mesothelioma, according to a study published in JAMA Oncology.1
Preclinical studies demonstrated that arginine deprivation is lethal to ASS1-negative cancers, including mesothelioma. Researchers evaluated the role of the arginine-lowering agent ADI-PEG20 in a randomized clinical trial.
For this multicenter, phase 2 ADAM trial, investigators enrolled 68 adults with advanced ASS1-deficient malignant pleural mesothelioma. Participants were randomly assigned 2:1 to ADI-PEG20 weekly plus best supportive care or best supportive care alone.
Median follow-up time was 38 months. ADI-PEG20 reduced the risk of progression death by 44%, in contrast with best supportive care alone (hazard ratio, 0.56; 95% CI, 0.33-0.96). Median progression-free survival was 3.2 months and 2.0 months, respectively.
There was no significant difference in life expectancy between the 2 treatment arms.
The most common symptomatic grade 3 or worse adverse events were immune related adverse reactions, nonfebrile neutropenia, gastrointestinal events, and fatigue. There was no significant difference in the incidence of these events overall.
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Longer period of arginine deprivation was associated with improved progression-free survival.
The findings suggest that arginine deprivation is safe; further clinical investigation of this approach in arginine-dependent cancers is warranted.
- Szlosarek PW, Steele JP, Nolan L, et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1–deficient malignant pleural mesothelioma. JAMA Oncol. 2016 Sep 1. doi: 10.1001/jamaoncol.2016.3049 [Epub ahead of print]