172PD - Final analysis: Phase II trial of irinotecan/S-1/cetuximab (IRIS/Cet) as second line treatment in patients with KRAS exon2 wild type metastatic col...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Gastrointestinal tumours
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter Takayuki Ando
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors T. Ando1, S. Yuki2, H. Nakatsumi3, T. Muranaka3, A. Hosokawa1, Y. Tsuji4, M. Nakamura5, O. Muto6, T. Sasaki7, I. Iwanaga8, K. Hatanaka9, A. Sato10, K. Eto11, K. Furukawa12, M. Tateyama13, Y. Takahashi14, S. Sogabe15, T. Honda16, Y. Sakata17, Y. Komatsu3
  • 1Gastroenterology And Hematology, Faculty Of Medicine, University of Toyama, 930-0194 - Toyama/JP
  • 2Gastroenterology And Hepatology, Hokkaido University Hospital, 060-8638 - Sapporo/JP
  • 3Cancer Center, Hokkaido University Hospital, 060-8638 - Sapporo/JP
  • 4Medical Oncology, KKR Tonan Hospital, Sapporo/JP
  • 5Gastroenterology, Sapporo City General Hospital, Sapporo/JP
  • 6Medical Oncology, Japanese Red Cross Akita Hospital, Akita/JP
  • 7Internal Medicine, Hokkaido Gastroenterology Hospital, 065-0041 - Sapporo/JP
  • 8Medical Oncology, Japanese Red Cross Kitami Hospital, 090-0026 - Kitami/JP
  • 9Gastroenterology, Hakodate Municipal Hospital, 041-0821 - Hakodate/JP
  • 10Medical Oncology, Hirosaki University Hospital, 036-8562 - Hirosaki/JP
  • 11Gastroenterology, Tomakomai City Hospital, 053-0034 - Tomakomai/JP
  • 12Gastroenterology, Niigata City General Hospital, Niigata/JP
  • 13Internal Medicine, Tomakomai Nisshou Hospital, 053-0803 - Tomakomai/JP
  • 14Gastroenterology, Hokkaido Cancer Center, Sapporo/JP
  • 15Medical Oncology, Kushiro Rosai Hospital, 085-8533 - Kushiro/JP
  • 16Gastroenterology And Hepatology, Nagaski University Hospital, 852-8501 - Nagasaki/JP
  • 17Ceo, Misawa City Hospital, Misawa/JP

Abstract

Background

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 mCRC. Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]).

Methods

Eligibility includes histologically confirmed mCRC, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on day 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 RR 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 and OS.

Results

Between Mar 2010 and Sep 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician’s choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW and 31.8% in the BW (p = 1.000). Median PFS was 4.2 months in the EW and 6.1 months in the BW (HR 0.752, p = 0.350). Median OS was 8.9 months in the EW and 10.7 months in the BW (HR 0.902, p = 0.737). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW vs 52.2% in the BW: p = 0.005) and stomatitis (2.9% in the EW vs 30.4% in the BW group: p = 0.046), these were significantly more common in the BW.

Conclusions

IRIS/Cet appeared to be highly effective with RR, PFS and OS in the both treatment schedule. Diarrhea and stomatitis were significantly more common in the BW. Therefore, in case of treatment with IRIS/Cet should be administered in the EW.

Clinical trial indentification

This trial did not have the trial protocol number (NIH or European equivalent).

Legal entity responsible for the study

Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group

Funding

Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group

Disclosure

S. Yuki: Honoraria: Taiho Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eli Lilly Japan. Y. Tsuji: Y.TSUJI has received honoraria from Merck Serono, Eli Lilly Japan, Chugai, Taiho, Ono, Takeda, Daiichi Sankyo, Kyowa Kirin, Yakult, Nippon Kayaku and Medicon, outside the submitted work. Y. Sakata: Honoraria: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Merck Serono, Ono Pharmaceutical, Nikkei Business Publications. Y. Komatsu: Honoraria and/or Research fund: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Kureha Corporation. All other authors have declared no conflicts of interest.