Arginine deprivation is a novel anticancer strategy in argininosuccinate synthetase 1 (ASS1)–negative tumors. In a multicenter, phase II trial, immunohistochemistry identified 68 patients with ASS1 deficiency among 201 patients with malignant pleural mesothelioma (MPM). The ASS1-deficient patients were randomized in a 2:1 ratio to either best supportive care (BSC) or BSC plus intramuscular ADI-PEG20, a pegylated arginine deiminase that causes arginine deprivation, at 36.8 mg/m2 weekly (in 4-week cycles) for up to 6 months. Of the ADI-PEG20 recipients, 23% received six treatment cycles.
During a median follow-up of 38 months, no participants had partial or complete response. However, stable disease at 4 months (using modified Response Evaluation Criteria in Solid Tumors [RECIST]) was significantly more common with ADI-PEG20 than with BSC alone (52% vs. 22%). ADI-PEG20 also outperformed BSC alone significantly in median progression-free survival (PFS; 3.2 vs. 2.0 months; hazard ratio, 0.56) and nonsignificantly in median overall survival (11.5 vs. 11.1 months) and life expectancy (15.7 vs. 12.1 months). The most common ADI-PEG20 toxicities were grade 1–2 nonfebrile neutropenia, gastrointestinal events, injection-site reactions, and fatigue; grade 3 events, in 25% of ADI-PEG20 recipients, were anaphylaxis and serum sickness. The two treatment groups had similar quality of life (whether patient- or observer-reported).
[Article continues at original source]
Asbestos-Mesothelioma Case Evaluation Form
Free. Confidential. No Obligation.