medwireNews: Findings from the AXEPT trial indicate that the overall survival (OS) of Asian patients with metastatic colorectal cancer (CRC) is similar whether they are given a modified (m)XELIRI (capecitabine plus irinotecan) regimen or FOLFIRI (leucovorin, fluorouracil and irinotecan), regardless of whether bevacizumab is also used.
“The results of this study suggest 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 colorectal cancer, at least for Asian populations”, say Tae Won Kim, from University of Ulsan College of Medicine in Seoul, South Korea, and co-workers.
After a median follow-up of 15.8 months, median OS was 16.8 months for the 326 patients given mXELIRI, consisting of irinotecan 200 mg/m2 on day 1 of a 21-day cycle plus capecitabine 800 mg/m2 twice daily on days 1–14, with or without bevacizumab 7.5 mg/kg on day 1.
This OS met noninferiority criteria compared with the median OS of 15.4 months for the 324 patients who received FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 and fluorouracil 400 mg/m2) on day 1 plus a 46-hour infusion of fluorouracil 2400 mg/m2 every 14 days. Patients may also have received bevacizumab 5 mg/kg on day 1.
“[A]dministration of mXELIRI requires only one visit per 3-week cycle for a 2-h or 3-h infusion, which has a notable advantage compared with the FOLFIRI regimen in terms of convenience for clinical staff and a substantial proportion of patients who prefer freedom from infusion pumps, fewer hospital visits, and fewer interruptions of work or daily activities”, the authors highlight in The Lancet Oncology.
In per protocol safety analysis, neutropenia was the most common grade 3 or 4 event in both arms, affecting 17% of mXELIRI-treated patients and 43% of those given FOLFIRI. By contrast, grade 3 or 4 diarrhoea was more common with XELIRI than FOLFIRI, at 7% versus 3%.
Serious adverse events affected 15% of the mXELIRI and 20% of the FOLFIRI patient groups; there were two deaths related to treatment with mXELIRI (pneumonitis and lung infection) and one death associated with FOLFIRI (lung infection).
Reviewing the findings from the phase III study of patients from Japan, South Korea and China, commentator Timothy Price, from the University of Adelaide in South Australia, questions whether the findings will transfer to non-Asian patients.
Recognising that primary tumour side is now a guide for biological treatment in CRC, he notes that mXELIRI is “unlikely to be appropriate” for left-sided RAS wild-type patients because of the potential negative interaction between capecitabine and anti-EGFR agents.
Discussing patients with right-sided tumours wild-type for RAS, “if irinotecan is preferred in the first-line setting then FOLFIRI would be the suggested regimen with an anti-EGFR antibody”, the commentator suggests, adding that first-line anti-EGFR agent plus FOLFOX would allow for second-line mXELIRI plus bevacizumab.
“However, for patients with the RAS mutation, the decision is less complex when a schedule of mXELIRI or CAPOX plus bevacizumab could be considered as the first-line treatment, especially when considering patients' quality of life, because these schedules overcome the need for infusion pumps and possibly port insertion”, Timothy Price writes.
“Furthermore in some settings, the economic benefit of a schedule that does not require pumps, pump disconnection, and additional time spent in the infusion or chemotherapy suite will be very attractive.”
Xu R-H, Muro K, Morita S, et al. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either way or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol; Advance online publication 16 March 2018.
Price TJ. Modified XELIRI (capecitabine plus irinotecan) for metastatic colorectal cancer. Lancet Oncol; Advance online publication 16 March 2018.
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