Modified capecitabine plus irinotecan (mXELIRI) was well-tolerated and yielded similar outcomes to leucovorin, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for Asian patients with metastatic colorectal cancer (CRC), according to a study published in Lancet Oncology.1
Full-dose XELIRI for metastatic CRC is associated with excessive gastrointestinal toxicity, though phase 2 trials suggest that a modified reduced-dose XELIRI may be better tolerated. The purpose of this trial was to determine the efficacy and safety of mXELIRI as a second-line therapy for CRC in an Asian population.
The open-label, non-inferiority, phase 3 AXEPT trial randomly assigned 650 Asian patients with unresectable CRC treated with prior chemotherapy to receive mXELIRI or FOLFIRI, both with or without bevacizumab, with a median follow-up of 15.8 months. The median age at baseline was 61, most patients had an Eastern Cooperative Oncology Group performance status of 0 to 1, and 62% had liver metastases.
mXELIRI was non-inferior to FOLFIRI, with a median overall survival of 16.8 months (95% CI, 15.3-19.1) vs 15.4 months (95% CI, 13.0-17.7), respectively (hazard ratio [HR], 0.85; 95% CI, 0.71-1.02; P < .0001).
Median progression-free survival was 8.4 months (95% CI, 7.1-9.1) with mXELIRI and 7.2 months (95% CI, 6.6-8.5) with FOLFIRI (HR, 0.95; 95% CI, 0.81-1.11; P = .51). The overall response rate was, however, higher in the mXELIRI arm, with 24.2% of patients responding vs 18.4% with FOLFIRI.
Responses were not stratified by bevacizumab treatment.
Delay in treatment and discontinuation due to adverse events occurred more frequently with FOLFIRI vs mXELIRI. Grade 3 to 4 neutropenia and diarrhea, however, were more frequent in the mXELIRI group. Treatment-related deaths due to pulmonary complications occurred in both the mXELIRI (2 patients) and FOLFIRI (1 patient) groups.
The authors concluded that “mXELIRI might be an effective, well tolerated, and more convenient alternative to FOLFIRI as a standard second-line backbone therapy for patients with metastatic CRC, at least for Asian populations.”
- 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, randomized, non-inferiority, phase 3 trial. Lancet Oncol. 2018 March 16. doi: 10.1016/S1470-2045(18)30140-2 [Epub ahead of print]