News & Perspective

AXEPT shows that the modified XELIRI regimen was non-inferior to standard FOLFIRI

1 year ago, OP Editor

Although intravenous fluorouracil (5-FU) has been the mainstay of chemotherapy for metastatic colorectal cancer (mCRC) for around half a century, efforts have been made to replace it with oral fluorinated pyrimidines to simplify the treatment process.1 At the recent ESMO Asia 2017 Congress, encouraging results have shown that the modified capecitabine and irinotecan (mXELIRI) regimen might be able to replace leucovorin, 5-FU, and irinotecan (FOLFIRI) regimen as a standard second-line backbone treatment for mCRC.2,3

A phase III randomized, controlled trial has previously compared XELIRI and FOLFIRI in previously untreated mCRC patients.4 However, XELIRI failed to replace FOLFIRI due to substantial toxicities, including severe vomiting, diarrhea, and dehydration.4 “Capecitabine is given orally and is more convenient for patients compared to infusional 5-FU. However, at the maximum doses, the combination of capecitabine and irinotecan (XELIRI) can be quite toxic,” commented Dr. Rodrigo Dienstmann of the Vall d’Hebron Institute of Oncology in Spain.3

In the multicenter, open-label, randomized phase III Asian XELIRI Project (AXEPT), 650 patients with histologically confirmed unresectable colorectal adenocarcinoma were randomized to receive mXELIRI ± bevacizumab every three weeks or FOLFIRI ± bevacizumab every two weeks.2,3 The mXELIRI regimen was previously developed with reduced doses of irinotecan (200mg/m2 on day 1) and capecitabine (1,600mg/m2 on days 1–14).2,3

The results of AXEPT, presented at the ESMO Asia 2017 Congress, has shown that mXELIRI ± bevacizumab was well-tolerated and had a non-inferior overall survival (OS) to FOLFIRI ± bevacizumab.2,3

After a median follow-up of 15.8 months, the median OS was 16.8 and 15.4 months in the mXELIRI and FOLFIRI arms, respectively (HR=0.85, 95% CI: 0.71–1.02, non-inferiority test p<0.0001).2,3 The mXELIRI arm has also demonstrated a favorable safety profile, since the incidence of grade 3/4 adverse events was significantly lower than the FOLFIRI arm (167 [53.9%] vs. 224 [72.3%] of 310 patients; p<0.0001).2,3

Patients were also stratified according to: (1) country (Japan vs. South Korea vs. China), (2) Eastern Cooperative Oncology Group (ECOG) performance status (0–1 vs. 2), (3) number of metastatic sites (one vs. more than one), (4) prior oxaliplatin treatment (yes vs. no), and (5) concurrent bevacizumab treatment (with vs. without), and the results were similar across all prespecified subgroups.2,3

“The main objective of AXEPT was to assess whether a reduced dose-intensity of the chemotherapy (the modified XELIRI regimen) would not negatively impact overall survival,” commented Dr. Dienstmann,“ as the trial met the primary endpoint, we can say that mXELIRI is non-inferior to standard FOLFIRI (with or without bevacizumab). The toxicity profile was quite favorable for the modified regimen, with less neutropenia. The investigators observed slightly more diarrhea, as expected, but still acceptable. This study supports the use of mXELIRI in the second line setting, with the potential to increase patient convenience.”3

“The AXEPT trial demonstrates that mXELIRI with or without bevacizumab has a non-inferior efficacy to FOLFIRI with or without bevacizumab and is well-tolerated. The mXELIRI regimen could be an alternative to the standard FOLFIRI regimen as a second line backbone therapy for mCRC.” concluded Dr. Tae Won Kim, Professor of the Department of Oncology at Asan Medical Center, South Korea.3



  1. Hirsch BR, Zafar SY. Capecitabine in the management of colorectal cancer. Cancer Manag Res. 2011;3:79-89.
  2. Kim TW, Park YS, Muro K, et al. Randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer (mCRC), comparing the efficacy and safety of XELIRI + bevacizumab versus FOLFIRI + bevacizumab (AXEPT). ESMO Asian 2017 Congress. 19 November 2017; Singapore. LBA3_PR.
  3. Study Shows New Second Line Therapy for Metastatic Colorectal Cancer is Effective and Safe. ESMO Asia 2017 Press Release. 2017 (Accessed December 28, 2017, at
  4. Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779-86.


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