P-269 - Phase II trial of Irinotecan/S-1 (IRIS) with Cetuximab (IRIS/Cet) as second line treatment in patients with KRAS WT metastatic colorectal cancer: HG...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter K. Hatanaka
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors K. Hatanaka1, H. Okuda2, M. Nakamura3, I. Iwanaga4, S. Yuki5, Y. Komatsu5, H. Nakatsumi5, A. Hosokawa6, O. Muto7, T. Meguro8, Y. Tsuji9, A. Sato10, K. Eto11, K. Furukawa12, M. Onodera13, M. Tateyama14, Y. Takahashi15, M. Dazai16, S. Yokoyama17, T. Honda18, M. Kudo19, Y. Sakata20
  • 1Hakodate Municipal Hospital, Hakodate/JP
  • 2Keiyukai Sapporo Hospital, Sapporo/JP
  • 3Sapporo City General Hospital, Sapporo/JP
  • 4Japanese Red Cross Kitami Hospital, Kitami/JP
  • 5Hokkaido University Hospital, Sapporo/JP
  • 6University of Toyama, Toyama/JP
  • 7Japanese Red Cross Akita Hospital, Akita/JP
  • 8Hokkaido Gastroenterology Hospital, Sapporo/JP
  • 9Tonan Hospital, Sapporo/JP
  • 10Hirosaki University Graduate School of Medicine, Hirosaki/JP
  • 11Tomakomai City Hospital, Tomakomai/JP
  • 12Niigata City General Hospital, Niigata/JP
  • 13Abashiri Kosei General Hospital, Abashiri/JP
  • 14Tomakomai Nisshou Hospital, Tomakomai/JP
  • 15Hokkaido Cancer Center, Sapporo/JP
  • 16Kushiro Rosai Hospital, Kushiro/JP
  • 17Kumamoto City Hospital, Kumamoto/JP
  • 18Nagasaki University Hospital, Nagasaki/JP
  • 19Sapporo Hokuyu Hospital, Sapporo/JP
  • 20Misawa City Hospital, Misawa/JP



HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of irinotecan, S-1 (IRIS) plus cetuximab as second line treatment in patients with KRAS exon2 wild type metastatic colorectal cancer (mCRC). Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014 Congress). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]).


Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients (pts) received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on days 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 as loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher's exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS, OS, and TTF.


Between Mar 2010 and Sep 2013, 58 pts were enrolled. One patient had no treatment (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW group and 31.8% in the BW group (p = 1.000). Median PFS was 4.2 months (95% CI 3.5–4.9) in the EW group and 6.1 months (4.1-8.1) in the BW group (HR 0.752, 95% CI 0.413–1.372, p = 0.350). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW group vs 52.2% in the BW group: p = 0.005) and stomatitis (2.9% in the EW group vs 30.4% in the BW group: p = 0.046), these were significantly more common in the BW group.


IRIS/Cet appeared to be highly effective with RR and PFS in the both treatment schedule, and also had met the primary endpoint. Diarrhea and stomatitis were significantly more common in the BW group. Therefore, in case of treatment with IRIS, cetuximab should be administered weekly. The final analysis will be presented in European Cancer Congress 2015.