Modified XELIRI vs FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer
In an Asian phase III noninferiority trial (AXEPT) reported in The Lancet Oncology, Xu et al found that modified XELIRI (mXELIRI, capecitabine plus irinotecan) was noninferior in overall survival vs standard FOLFIRI (leucovorin, fluorouracil, and irinotecan), both given with or without bevacizumab (Avastin), as second-line treatment of metastatic colorectal cancer.
Study Details
In the open-label trial, 650 patients from 98 sites in China, Japan, and South Korea were randomized between December 2013 and August 2015 to receive mXELIRI with or without bevacizumab (n = 326) or FOLFIRI with or without bevacizumab (n = 324). Use of bevacizumab was at investigator and patient discretion. Overall, 83% of the mXELIRI group and 84% of the FOLFIRI group received bevacizumab.
The mXELIRI group received irinotecan at 200 mg/m² on day 1 plus oral capecitabine at 800 mg/m² twice daily on days 1 to 14 every 21 days with or without bevacizumab at 7.5 mg/kg on day 1. The FOLFIRI group received irinotecan at 180 mg/m² on day 1, leucovorin at 200 mg/m² on day 1, fluorouracil at 400 mg/m² on day 1 and a 46-hour continuous infusion of fluorouracil (2,400 mg/m²) repeated every 14 days with or without bevacizumab at 5 mg/kg on day 1.
Randomization was stratified by country, Eastern Cooperative Oncology Group performance status, number of metastatic sites, previous oxaliplatin treatment, and concomitant bevacizumab treatment. The primary endpoint was overall survival in the intention-to-treat analysis. Noninferiority was established by an upper margin of the 95% confidence interval (CI) for the hazard ratio (HR) of ≤ 1.30.
Overall Survival
Median follow-up was 15.8 months. Median overall survival was 16.8 months in the mXELIRI group vs 15.4 months in the FOLFIRI group (HR = 0.85, 95% CI = 0.71–1.02, P < .0001 for noninferiority). The prespecified test for superiority at a 95% CI upper margin of 1.0 was not significant (P = .088). Median progression-free survival was 8.4 months vs 7.2 months (HR = 0.95, P = .51).
Objective response was observed in 24% vs 18% of patients. After progression, 60% of the mXELIRI group and 58% of the FOLFIRI group received subsequent treatment, including anti-EGFR agents with or without irinotecan in 18% and 16%.
Adverse Events
Grade ≥ 3 adverse events occurred in 54% of the mXELIRI group vs 72% of the FOLFIRI group, with the most common in both groups being neutropenia (17% vs 43%). Grade 3 or 4 diarrhea was more common in the mXELIRI group (7% vs 3%).
Serious adverse events occurred in 15% of the mXELIRI group vs 20% of the FOLFIRI group. Treatment-related death occurred in two patients in the mXELIRI group (due to pneumonitis and lung infection) and one patient in the FOLFIRI group (due to lung infection).
The investigators concluded, “mXELIRI with or without bevacizumab is well tolerated and non-inferior to FOLFIRI with or without bevacizumab in terms of overall survival. mXELIRI could be an alternative to FOLFIRI as a standard second-line backbone treatment for metastatic colorectal cancer, at least for Asian patient populations.”
The study was funded by Chugai Pharmaceutical and F. Ho?mann-La Roche.
Tae Won Kim, MD, of Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author for The Lancet Oncology article.
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