Heinz-Josef Lenz1, Donna Niedzwiecki2, Federico Innocenti3, Charles Blanke4 et al.

501O - CALGB/SWOG 80405: PHASE III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with expanded ras analyses untreated metastatic adenocarcinoma of the colon or rectum (MCRC). 



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).


Updated analysis will be shown at meeting (see SLIDES).


All patients with newly diagnosed mCRC should be tested for ras. Overall survival >30 months in both arms sets a new benchmark for patients with mCRC which was achieved across a broad clinical trials network and suggests that the results apply in a variety of practice settings. 1st-line therapy should reflect treatment goal and concern for potential side effects. With additional data such as dose intensity, treatment duration, location, tumor shrinkage, 2nd-line therapies and additional biomarkers for anti-EGFR and anti VEGF therapies we might understand better the differencies between FIRE3 and 80405.