Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial.
OBJECTIVE
To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC).


METHODS
Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117).


RESULTS
No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56% vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated.


CONCLUSIONS
This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.
Ocvirk
Janja
J
Institute of Oncology, 1000 Ljubljana, Slovenia.
Brodowicz
Thomas
T
Wrba
Fritz
F
Ciuleanu
Tudor E
TE
Kurteva
Galina
G
Beslija
Semir
S
Koza
Ivan
I
Pápai
Zsuzsanna
Z
Messinger
Diethelm
D
Yilmaz
Ugur
U
Faluhelyi
Zsolt
Z
Yalcin
Suayib
S
Papamichael
Demetris
D
Wenczl
Miklós
M
Mrsic-Krmpotic
Zrinka
Z
Shacham-Shmueli
Einat
E
Vrbanec
Damir
D
Esser
Regina
R
Scheithauer
Werner
W
Zielinski
Christoph C
CC
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin