501O - CALGB/SWOG 80405: PHASE III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuxi...

Date 29 September 2014
Event ESMO 2014
Session Anti-EGFR or anti-VEGF in first-line RAS wild-type metastastic CRC patients: Can we define an "optimal" treatment strategy?
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Heinz-Josef Lenz
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors H. Lenz1, D. Niedzwiecki2, F. Innocenti3, C. Blanke4, M.R. Mahony5, B.H. O'Neil6, J.E. Shaw7, B. Polite8, H. Hochster9, J. Atkins10, R. Goldberg11, R. Mayer12, R.L. Schilsky13, M. Bertagnolli14, A. Venook15
  • 1Division Of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 2Biostatistics, Duke University, Durham/US
  • 3Pharmacology, University of North Carolina, Chapel Hill/US
  • 4Medicine, Oregon Health Science University, Portland/US
  • 5Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester/US
  • 6Hematology And Oncology, Indiana University, 46202 - Indianapolis/US
  • 7Massey Cancer Center, Virginia Commonwealth University Med. Ctr., US-23298 - Richmond/US
  • 8Medical Oncology, University of Chicago, Chicago/US
  • 9None, Yale Cancer Center, New Haven/US
  • 10-, Southeastern Medical Oncology Center, Goldsboro/US
  • 11Division Of Medical Oncology, Ohio State University School of Medicine, James Cancer Hospital and Solove Research Institute, Columbus/US
  • 12., Dana-Farber Cancer Institute, Boston/US
  • 13Medicine, The University of Chicago Medical Centre, US-60637-1470 - Chicago/US
  • 14Surgery, Brigham and Women's Hospital, Boston/US
  • 15Division Of Medical Oncology, University of California San Francisco, San Francisco/US



FOLFIRI or mFOLFOX6, combined with BV or CET, are 1st-line treatments for MCRC. The optimal antibody combination is unknown.


Pts with RAS wt (codons 12 and 13) MCRC and performance status 0-1 received FOLFIRI or mFOLFOX6 (MD/pt choice at enrollment) and randomized to either CET 400 mg/m2 X 1, then 250 mg/m2 qw or BV 5 mg/kg q2w. The original study included unselected MCRC pts receiving FOLFIRI or mFOLFOX6 and randomized to CET, BV or both. After 1420 pts accrued the study amended as follows: only pts w/ KRAS wt tumors (codon 12 and 13) were included. Accrual goal was 1142 pts Expanded RAS was tested in all wt ras exon 2 using beaming technology including KRAS exon 3,4 and NRAS exon 2, 3 and 4 with a detection sensitivity of 0.01%. Subsequent Rx not mandated. 1° endpoint was overall survival (OS).


Between 11/2005 and 3/2012, 3058 unselected pts enrolled, 2334 KRAS wt pts randomized; final N =1137 (333 pre-amend eligible retrospective KRAS test, 804 post-amend), median f/u = xx mos; Median age–59 y; 61% male. Chemo/BV–559; chemo/CET–578. FOLFIRI = 26.6%, mFOLFOX6 = 73.4%. From xx patients tumor samples were available for expanded ras analyses. We identified xx% mutations in kras exon 3 and 4 and NRAS in exon 2,3 and 4 in patients with wt KRAS exon2. The OS in patients with wt RAS treated with chemo/BV v. chemo/CET = xx (xx - xx) v. xx (xx - x) mos; HR = xx (xx, xx) (p value = xxx). PFS (by investigator): chemo/BV v. chemo/CET: xxx (xx - xx) v. xxx (xx - xx) mos. On-study toxicity and deaths as expected.


Updated analysis will be shown at meeting.


H. Lenz: Ad Board Genentech/Roche, MerckKG, EMD, BMS. All other authors have declared no conflicts of interest.