Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

Abstract

Aim: 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.

Conclusion: 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.

Figure 1

Disposition of patients as of clinical cut-off date January 2008. The intention to treat (ITT) population comprised 77 patients randomized to FOLFOX6 plus cetuximab and 74 randomized to FOLFIRI plus cetuximab. ¹Values based on all treated patients (n = 151). FOLFOX: 5-fluorouracil (5-FU) folinic acid (FA) and oxaliplatin; FOLFIRI: 5-FU FA and irinotecan; PD: Progressive disease; AE: Adverse event.

Figure 2

Kaplan Meier estimates for progression-free survival. A: By treatment group in the ITT population, FOLFOX6 plus cetuximab (n = 77) vs FOLFIRI plus cetuximab (n = 74); B: By KRAS mutation status in the KRAS population, KRAS wild-type (n = 62) vs KRAS mutation (n = 55); C: By tumor KRAS mutation status in patients receiving FOLFOX6 plus cetuximab, KRAS wild-type (n = 34) vs KRAS mutation (n = 23); D: By tumor KRAS mutation status in patients receiving FOLFIRI plus cetuximab, KRAS wild-type (n = 28) vs KRAS mutation (n = 32).

Figure 3

Kaplan Meier estimates for survival. A: By treatment group in the ITT population, FOLFOX6 plus cetuximab (n = 77) vs FOLFIRI plus cetuximab (n = 74); B: By tumor KRAS mutation status, KRAS wild-type (n = 62) vs KRAS mutation (n = 55); C: By KRAS mutation status in patients receiving FOLFOX6 plus cetuximab, KRAS wild-type (n = 34) vs KRAS mutation (n = 23); D: By tumor KRAS mutation status in patients receiving FOLFIRI plus cetuximab, KRAS wild-type (n = 28) vs KRAS mutation (n = 32).