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).
SLIDES |
Aim
FOLFIRI or mFOLFOX6, combined with BV or CET, are 1st-line treatments for MCRC. The optimal antibody combination is unknown.
Methods
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).
Results
Updated analysis will be shown at meeting (see SLIDES).
Conclusion
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.