Modified XELIRI Noninferior to FOLFIRI for OS in Metastatic Colorectal Cancer

The modified XELIRI regimen (mXELIRI) is noninferior to FOLFIRI, both with or without bevacizumab, in regards to overall survival (OS) among patients with metastatic colorectal cancer, according to research published in The Lancet Oncology.

The XELIRI regimen has not been recommended as a first- or second-line therapy for metastatic colorectal cancer due to severe gastrointestinal toxicity, but data from previous studies suggested that mXELIRI may be effective and well tolerated.

For the noninferiority phase 3 AXEPT study, researchers randomly assigned 650 patients to receive mXELIRI (IV irinotecan 200 mg/m², oral capecitabine 800 mg/m² twice daily, with or without bevacizumab 7.5 mg/kg) or FOLFIRI (IV irinotecan 180 mg/m², IV leucovorin 200 mg/m², fluorouracil 2400 mg/m² with or without bevacizumab 5 mg/kg) in multiple study sites throughout Asia. Eligible patients had unresectable colorectal adenocarcinoma, and had withdrawn from first-line chemotherapy for metastatic colorectal cancer.   

After a median follow-up of 15.8 months, the median OS for patients in the mXELIRI arm was 16.8 months vs 15.4 months for the FOLFIRI arm (P <.0001); 242 patients in the mXELIRI and 248 patients in the FOLFIRI arm died.

The most commonly observed grade 3 to 4 adverse event was neutropenia (17% vs 43%; mXELIRI vs FOLFIRI) and diarrhea (7% vs 3%); serious adverse events were reported in 15% of patients in the mXELIRI group and 20% in the FOLFIRI group.

Results showed that the reduced-dose mXELIRI regimen was noninferior to standard FOLFIRI in terms of OS. The authors concluded that “mXELIRI could be an alternative to FOLFIRI as a standard second-line backbone treatment for metastatic colorectal cancer, at least for Asian patient populations.”

Reference

Xu RH, Muro K, Morita S, et al. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial [published online March 16, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30140-2