Metastatic pancreatic adenocarcinoma is a challenging disease with limited treatment options. The FOLFIRINOX regimen (FFX; fluorouracil, oxaliplatin, irinotecan, and leucovorin) is a standard first-line therapy for patients with a good performance status and organ function. Devimistat combined with modified FFX (mFXX) demonstrated safety and promising efficacy in a prior phase I trial. The global phase III AVENGER 500 trial assessed the efficacy and safety of devimistat in combination with mFFX compared to standard-dose FFX in treatment-naïve patients with metastatic pancreatic adenocarcinoma.1
METHODS
A total of 528 patients with treatment-naïve metastatic pancreatic adenocarcinoma were randomised in a 1:1 ratio to receive devimistat combined with mFFX or standard-dose FFX. Treatments were given every two weeks until disease progression or intolerable toxicity. Devimistat was administered intravenously at 500 mg/m² total per day on days 1 and 3. The primary endpoint was overall survival (OS).
RESULTS
The median OS was 11.1 months for the devimistat plus mFFX arm vs 11.7 months for the FFX arm (HR[95% CI]: 0.95[0.77-1.18], p = 0.655). Median progression-free survival (PFS) was 7.8 months and 8.0 months, respectively (HR[95% CI]: 0.99[0.76-1.29], p= 0.94). Grade ≥3 treatment-emergent adverse events occurring in >10% of patients in the devimistat plus mFFX arm vs the FXX arm included neutropenia (29.0% vs 34.5%), diarrhoea (11.2% vs 19.6%), hypokalaemia (13.1% vs 14.9%), anaemia (13.9% vs 13.6%), thrombocytopenia (11.6% vs 13.6%), and fatigue (10.8% vs 11.5%).
CONCLUSIONS
Adding devimistat to mFFX did not improve survival outcomes in metastatic pancreatic adenocarcinoma compared to standard-dose FFX. The addition of devimistat showed no unexpected safety concerns.
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