FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer-subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306.
BACKGROUND
The AIO KRK-0306 trial compares the efficacy of infusional 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC). In October 2008, an amendment terminated the inclusion of patients with KRAS-mutated tumours. This subgroup of patients is evaluated in the present analysis, while the study is ongoing for patients with KRAS wild-type tumours.


METHODS
Patients were randomly assigned to FOLFIRI (Tournigand regimen) every 2 weeks plus cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly=arm A) or bevacizumab (5 mg/kg every 2 weeks=arm B). Among 336 randomised patients, KRAS mutation was demonstrated in 100 assessable patients. The primary study end point was objective response rate (ORR).


RESULTS
ORR was 44% [95% confidence interval (CI) 29% to 59%] in arm A versus 48% (95% CI, 33% to 62%) in arm B. Progression-free survival was 7.5 versus 8.9 months (hazard ratio: 1.0) and overall survival was 22.7 versus 18.7 months (hazard ratio: 0.86) in arms A versus B, respectively.


CONCLUSIONS
This is the first head to head comparison of cetuximab versus bevacizumab in first-line treatment of mCRC. In the present evaluation of patients with KRAS-mutated tumours, neither strategy demonstrated a clearly superior outcome.
Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
S
S
Stintzing
L
L
Fischer von Weikersthal
T
T
Decker
U
U
Vehling-Kaiser
E
E
Jäger
T
T
Heintges
C
C
Stoll
C
C
Giessen
D P
DP
Modest
J
J
Neumann
A
A
Jung
T
T
Kirchner
W
W
Scheithauer
V
V
Heinemann
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005858:Germany; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D028761:Withholding Treatment; D018631:ras Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003062:Codon; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin