P-0211 - Prespecified subgroup analyses in WJOG4407G trial, a randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab in firs...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Hiroshi Tamagawa
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors H. Tamagawa1, E. Shinozaki2, K. Nakashima3, K. Yamaguchi4, M. Ando5, K. Yamazaki6, S. Morita7, K. Suyama8, N. Boku9, M. Okabe10, I. Hyodo11, K. Suzuki12, N. Seki13, K. Kawakami14, M. Sato15, Y. Takahashi16, T. Hirashima17, M. Ebi18, T. Otsuji19, F. Tamura20
  • 1Osaka General Medical Center, Osaka/JP
  • 2Depertment of Gastroenterology, Cancer Institute Hospital of JFCR, Koto-ku/JP
  • 3First Department of Internal Medicine Faculty of Medicine, University of Miyazaki, Miyazaki/JP
  • 4Saitama Cancer Center, Kita-adachi-gun/JP
  • 5Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya/JP
  • 6Shizuoka Cancer Center, Sunto-gun/JP
  • 7Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto/JP
  • 8Department of Medical Oncology, Toranomn Hospital, Minato-ku/JP
  • 9Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki/JP
  • 10Department of Surgery, Kurashiki Central Hospital, Kurashiki/JP
  • 11Division of Gastroenterology, University of Tsukuba, Tsukuba/JP
  • 12Department of Gastroenterology, Kushiro City General Hospital, Kushiro/JP
  • 13Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku/JP
  • 14Division of Gastroenterology, Muroran City General Hospital, Muroran/JP
  • 15Department of Gastroenterology and Hepatology, Ryuugasaki Saiseikai Hospital, Ryugasaki/JP
  • 16Department of Gastroenterology, Hokkaido Cancer Center, Sapporo/JP
  • 17Osaka Prefectural Medical Center for Respiratory and Allergic, Habikino/JP
  • 18Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya/JP
  • 19Department of Internal Medicine, Dongo Hospital, Yamatotakada/JP
  • 20Kumamoto Regional Medical Center, Kumamoto/JP



WJOG4407G trial has demonstrated that FOLFIRI + bevacizumab (Bev) is non-inferior to mFOLFOX6 + Bev with respect to progression-free survival (PFS) in the 1st-line treatment for metastatic colorectal cancer (mCRC). In the present analyses, PFS of prespecified subgroups was evaluated to assess the consistency of treatment effect.


Patients (pts) with previously untreated mCRC were randomized to receive either mFOLFOX6 + Bev or FOLFIRI + Bev until disease progression or unacceptable toxicity occurred. The history of adjuvant chemotherapy with fluoropyrimidines more than 6 months before study entry was permitted. PFS was analyzed with respect to demographic and baseline characteristics (sex, age, ECOG performance status, number of metastatic sites, surgery for primary lesion, measurable lesion, KRAS codon12/13 mutation status, histological type, peritoneal metastasis, and site of primary lesion), and stratification factors (adjuvant chemotherapy and liver limited disease).


FOLFIRI + Bev showed slightly better PFS than mFOLFOX6 + Bev for all subgroups. For pts with prior history of adjuvant chemotherapy, FOLFIRI + Bev (n = 33) showed remarkably longer PFS than mFOLFOX6 + Bev (n = 31) (median PFS 19.4 v.s. 11.5 months, hazard ratio (HR) 0.551, 95% CI 0.308-0.987; p = 0.042). For pts without prior history of adjuvant chemotherapy, median PFS was 11.04 months for FOLFIRI + Bev (n = 164) and 10.74 months for mFOLFOX6 + Bev (n = 167) (HR 0.979, 95% CI 0.769-1.246; p = 0.860). KRAS mutation status was checked in 85.3% of pts. Median PFS was 11.20 months for FOLFIRI + Bev (n = 103) and 10.35 months for mFOLFOX6 + Bev (n = 96) (HR 0.881, 95% CI 0.649-1.20; p = 0.416) in KRAS wild type, and 16.59 and 11.40 months in KRAS mutant type (n = 66 and 72, HR 0.833, 95% CI 0.569-1.22; p = 0.345).


The non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev with respect to PFS as 1st-line treatment for mCRC was consistent among the all subsets, including KRAS mutation status.