Comparative Analysis of mFOLFIRINOX and mFOLFOX6 in HER2-Negative Gastric Cancer

In a recent presentation at the 2025 ESMO Gastrointestinal Cancers Congress, results from the phase 3 IRIGA trial were discussed, revealing mixed outcomes when comparing mFOLFIRINOX and mFOLFOX6 in patients with HER2-negative metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. The trial aimed to evaluate the efficacy and safety of these two chemotherapy regimens in a population of 326 patients who had not previously received systemic therapy for advanced disease.

The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and objective response rate (ORR). According to Dr. Daria Gavrilova, an oncologist at the Russian Federation, the results indicated that while mFOLFIRINOX improved the objective response rate significantly—31.2% compared to 19.3% for mFOLFOX6 (p = .014)—it did not yield a statistically significant improvement in PFS or OS for the overall cohort. The median PFS was reported as 7.20 months for mFOLFIRINOX versus 6.83 months for mFOLFOX6 (HR 0.81; 95% CI, 0.63-1.04; p = .266).

However, subgroup analysis revealed that patients with grade 1 or 2 disease who received mFOLFIRINOX experienced a significant benefit in PFS, with a median of 9.9 months compared to 8.4 months for those on mFOLFOX6 (HR 0.55; 95% CI, 0.30-0.99). This suggests that while the overall survival did not vary significantly between the two treatments, specific patient populations may benefit from the mFOLFIRINOX regimen.

Despite these findings, mFOLFIRINOX was associated with a higher incidence of treatment-related toxicities, particularly nausea, diarrhea, and vomiting. The safety profile of mFOLFIRINOX included increased rates of grade 1 to 2 adverse effects, which were significant in comparison to mFOLFOX6.

The IRIGA trial was conducted as a randomized, open-label study where participants were stratified by various factors including age, tumor characteristics, and performance status. Patients received chemotherapy in a defined regimen, with 180 mg/m² of irinotecan, 85 mg/m² of oxaliplatin, 200 mg/m² of leucovorin, and 250 mg/m² of 5-FU for mFOLFIRINOX, while those on mFOLFOX6 received a different regimen involving oxaliplatin and leucovorin.

As the medical community continues to explore effective treatments for HER2-negative gastric and GEJ adenocarcinoma, the findings from the IRIGA trial underscore the importance of personalized treatment approaches. The results suggest that while mFOLFIRINOX may offer better response rates, its higher toxicity levels necessitate careful consideration of patient selection and management strategies. The ongoing analysis of these treatment regimens will be crucial in optimizing therapeutic outcomes for patients battling this aggressive form of cancer.

This trial not only adds to the body of knowledge surrounding gastric cancer treatments but also highlights the need for continued research into the efficacy and safety of chemotherapy protocols, with patient quality of life remaining a critical component of cancer care. Further studies may provide additional insights into optimizing treatment strategies that balance efficacy with tolerability in this challenging patient population.