Adding pegargiminase to standard chemotherapy can improve outcomes in patients with chemotherapy-naïve, nonepithelioid pleural mesothelioma, according to research published in JAMA Oncology. [Szlosarek PW, Creelan BC, Sarkodie T, et al. Pegargiminase plus first-line chemotherapy in patients with nonepithelioid pleural mesothelioma. The ATOMIC-Meso randomized clinical trial. JAMA Oncol. Published online February 15, 2024. doi:10.1001/jamaoncol.2023.6789]
Researchers found that patients who received pegargiminase and standard chemotherapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received standard chemotherapy alone.
These results come from the phase 2-3 ATOMIC-Meso trial (ClinicalTrials.gov identifier: NCT02709512), which included 249 adults with chemotherapy-naïve, advanced nonepithelioid pleural mesothelioma.
The patients were randomly assigned to receive weekly pegargiminase at 36 mg/m2 (n=125) or placebo (n=124) for up to 24 months. Patients in both arms also received up to 6 cycles of pemetrexed plus cisplatin or carboplatin.
Baseline characteristics were generally well balanced between the arms. In the overall cohort, the median age was 71 (range, 28-86) years, 82.7% of patients were men, and 93.2% were White. All disease stages were represented. Few patients had received prior surgery (14.9%) or radiotherapy (5.2%).
All patients had a minimum follow-up of 12 months for survival. The median OS was 9.3 months in the pegargiminase arm and 7.7 months in the placebo arm (hazard ratio [HR], 0.71; 95% CI, 0.55-0.93; P =.02). The 1-year OS rate was 41.4% and 31.4%, respectively.
The median PFS was 6.2 months in the pegargiminase arm and 5.6 months in the placebo arm (HR, 0.65; 95% CI, 0.46-0.90; P =.02)….
“In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma,” the researchers wrote. “Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.”
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