by ecancer reporter Janet Fricker

Patients with KRAS exon 2 wild type metastatic colorectal cancer achieve longer overall survival with FOLFIRI plus cetuximab than FOLFIRI plus bevacizumab, concluded the FIRE-3 trial published in Lancet Oncology.

While cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown.

In the open-label, randomised, phase 3 FIRE- 3 trial Professor Volker Heinemann, from the University of Munich, and colleagues set out to explore whether cetuximab or bevacizumab was a more effective partner for FOLFIRI in first-line treatment of metastatic colorectal cancer.

Patients were initially recruited without regard to KRAS tumour mutation status.

However, following reports that cetuximab was not active in patients with tumour KRAS exon 2 mutations (codon 12 or 13) enrolment was restricted to patients without KRAS exon 2 mutations (wild type).

Between January 2007 and September 2012 752 patients from 116 centres in Germany and Austria were randomly assigned to a treatment group.

For the 593 patients with KRAS exon 2 wild-type tumours 297 were assigned to FOLFIRI plus cetuximab and 295 to FOLFIRI plus bevacizumab.

Results showed that 184 patients in the cetuximab group (62%) achieved an objective response compared with 171 in the bevacizumab group (58%) (OR 1·18, 95% CI 0·85–1·64; p=0·18).

Furthermore median progression free survival was 10 months in the cetuximab group versus10·3 months in the bevacizumab group (HR 1·06, 95% CI 0·88–1·26; p=0·55); however, median overall survival was 28·7 months in the cetuximab group compared with 25·0 months in the bevacizumab group (HR 0·77, 95% CI 0·62–0·96; p=0·017).

The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (affecting 25% of cetuximab patients versus 21% of bevacizumab patients), skin reactions (affecting 26% of cetuximab patients versus 2% of bevacizumab patients) and diarrhoea (affecting 11% of cetuximab patients versus 14% of bevacizumab patients).

“Our data suggest that FOLFIRI plus cetuximab should be the chosen first-line treatment regimen for patients with RAS wild-type metastatic colorectal cancer,” wrote the authors.

Reference

V Heinemann, L Fischer von Weikersthal, T Decker, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncology. Published online August 1, 2014.