Pegargiminase Confers Survival Benefit in Nonepithelioid Pleural Mesothelioma

Adding pegargiminase to standard chemotherapy can improve outcomes in patients with chemotherapy-naïve, nonepithelioid pleural mesothelioma, according to research published in JAMA Oncology.

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).

The objective response rate was 13.8% in the pegargiminase arm and 13.5% in the placebo arm (P =.95). The disease control rate at 12 weeks was 85.1% and 76.4%, respectively (P =.15).

Grade 3 or higher adverse events (AEs) related to pegargiminase or placebo occurred in 28.8% of patients in the pegargiminase arm and 16.9% of patients in the placebo arm (P =.03).

The most common of these grade 3 or higher AEs (in the pegargiminase and placebo arms, respectively) were decreased neutrophil counts (5.6% vs 1.6%), anemia (4.8% vs 2.4%), and neutropenia (4.8% vs 1.6%).

There were 7 fatal AEs in the pegargiminase arm and 12 in the placebo arm. Two of these AEs — 1 sudden death and 1 case of sepsis — were considered possibly related to pegargiminase. One death in the placebo arm — due to sepsis — was considered possibly related to treatment.

“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.”

Disclosures: This study was supported by Polaris Group. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor