Pegargiminase + Chemo Increases Survival Rate in Nonepithelioid Pleural Mesothelioma

FRIDAY, Feb. 23, 2024 (HealthDay News) -- For patients with nonepithelioid pleural mesothelioma, pegargiminase plus chemotherapy is associated with improved survival versus placebo plus chemotherapy, according to a study published online Feb. 15 in JAMA Oncology.

Peter W. Szlosarek, M.D., Ph.D., from Queen Mary University of London, and colleagues examined the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma in a phase 2 to 3 double-blind randomized clinical trial conducted at 43 centers in five countries. A total of 249 patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m²) or placebo. In addition, all patients received intravenous pemetrexed (500 mg/m²) and platinum chemotherapy every three weeks for up to six cycles.

The researchers found that median overall survival was 9.3 and 7.7 months with pegargiminase-chemotherapy and placebo-chemotherapy, respectively (hazard ratio [HR] for death, 0.71). The corresponding median progression-free survival was 6.2 and 5.6 months, respectively (HR, 0.65). Grade 3 to 4 adverse events occurred in 28.8 percent of patients with pegargiminase and 16.9 percent of patients with placebo. Drug hypersensitivity and skin reactions occurred in 2.4 and 1.6 percent of patients, respectively, in the pegargiminase arm versus none in the placebo arm.

"The pegargiminase-pemetrexed-platinum triplet was safe and validates arginine deprivation as a novel therapeutic antimetabolite strategy for patients with nonepithelioid mesothelioma," the authors write. "Additional studies of pegargiminase-based regimens are warranted in patients with other urea cycle-dysregulated cancers."

Several authors disclosed ties to pharmaceutical companies, including Polaris Group, which is developing pegargiminase and funded the study.

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