LBA3_PR - Randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer (mCRC), comparing the efficacy and safety...

Date 19 November 2017
Event ESMO Asia 2017 Congress
Session Proffered paper session 4
Topics Cytotoxic agents
Colon and Rectal Cancer
Gastrointestinal Cancers
Biological therapy
Presenter Tae Won Kim
Citation Annals of Oncology (2017) 28 (suppl_10): x186-x195. 10.1093/annonc/mdx729
Authors T.W. Kim1, Y.S. Park2, K. Muro3, R. Xu4, S. Han5, K. Yamazaki6, W. Wang7, J.B. Ahn8, H. Uetake9, Y. Deng10, S. Cho11, H. Matsumoto12, Y. Ba13, K. Lee14, T. Nishina15, T. Zhang16, S. Iwasa17, S. Morita18, J. Sakamoto19
  • 1Oncology, Asan Medical Center, 05505 - Seoul/KR
  • 2Hematology-oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 3Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 4State Key Laboratory Of Oncology In South China, Medical Oncology, Sun Yat-sen university cancer center, 510060 - Guangzhou/CN
  • 5Internal Medicine, Seoul National University Hospital, 03080 - Seoul/KR
  • 6Gastrointestinal Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 7Gastrointestinal Oncology, The First People's Hospital of Foshan, Guangdong/CN
  • 8Internal Medicine, Severance Hospital, Yonsei University, 120-752 - Seoul/KR
  • 9Specialized Surgeries, Graduate School, Tokyo Medical and Dental University, Tokyo/JP
  • 10Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou/CN
  • 11Hematology-oncology, Chonnam National University Hwasun Hospital, 58128 - Jeollanamdo/KR
  • 12Surgery, Tokyo metropolitan cancer and infectious diseases center Komagome hospital, Tokyo/JP
  • 13Digestive Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin/CN
  • 14Department Of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 13620 - Seongnam/KR
  • 15Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 16Abdominal Oncology, Union Hospital Tongji Medical College of Huazhong University of Science & Technology, Wuhan/CN
  • 17Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo/JP
  • 18Biomedical Statistics And Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto/JP
  • 19Director, Tokai Central Hospital, 504-8601 - Kakamigahara/JP



Capecitabine and irinotecan combination (XELIRI) regimen has not been recommended by major guidelines due to substantial toxicities. Recently, modified XELIRI (irinotecan 200 mg/m2 on day 1, capecitabine 1600 mg/m2 on days 1–14 every 3 weeks: mXELIRI) has shown favorable tolerability and efficacy with or without bevacizumab (BEV). We conducted “Asian XELIRI ProjecT” (AXEPT) to demonstrate the OS non-inferiority of XELIRI±BEV versus standard FOLFIRI±BEV as second-line chemotherapy for mCRC.


Patients with histologically confirmed mCRC, ECOG performance status (PS) 0–2, and disease progression or intolerance of the first-line regimen were eligible. Patients were randomized (1:1) to receive standard FOLFIRI±BEV (5 mg/kg on day 1), repeated every 2 weeks (FOLIRI arm) or mXELIRI±BEV (7.5 mg/kg on day 1) repeated every 3 weeks (mXELIRI arm). A total of 464 events were estimated as necessary to show OS non-inferiority with a power of 80% at a one-sided α of 0.025, requiring a target sample size of 600 patients. The 95% confidence interval upper limit of the hazard ratio was pre-specified as less than 1.3. Stratification factors included country, ECOG PS, number of metastatic sites, prior oxaliplatin treatment, and concomitant BEV treatment.


Between Dec 2013 and Aug 2015, 650 patients were enrolled and randomized either to receive mXELIRI±BEV (n = 326) or FOLFIRI±BEV (n = 324). After a median follow-up of 15.8 months (IQR; 8.7–24.9), median overall survival was 16.8 months in the mXELIRI arm and 15.4 months in the FOLFIRI arm (HR 0.85, 95% CI 0.71–1.02, non-inferiority test p 


mXELIRI±Bev is well-tolerated and non-inferior to FOLFIRI±Bev in terms of OS. mXELIRI could be an alternative to FOLFIRI as a standard second-line backbone treatment for mCRC.

Clinical trial identification

NCT01996306; UMIN000012263

Legal entity responsible for the study

This trial is supported by Epidemiological and Clinical Research Information Network (ECRIN: global sponsor).


This trial was funded by Chugai Pharmaceutical Co., Ltd. and F. Hoffmann-La Roche Ltd.


T.W. Kim: Research Fund: Roche, Merck Serono, Bayer. K. Muro: Research grants from MSD, Daiichi Sankyo, Ono, Shionogi, Kyowa Hakko Kirin, and Gilead Sciences, and also honoraria from Chugai, Takeda, Eli Lilly, Merck Serono, Taiho, and Yakult. K. Yamazaki: Honoraria: Takeda, Chugai, Taiho, Yakult, Merck Serono, Bristol Myers Squib, Lily, Sanofi, S. Morita: Honoraria from Chugai and Daiichi-Sankyo. All other authors have declared no conflicts of interest.