ESMO WCGC 2013 Report – OS though not PFS superior for FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in mCRC patients: Findings from FIRE-3

Dominik Modest, University Hospital, Grosshadern, Munch, Germany.  Overall survival (OS) in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC) who received first-line treatment with FOLFIRI plus cetuximab was significantly longer than those who received FOLFIRI plus bevacizumab despite having virtually identical progression-free survival (PFS) rates, a phase III randomized study shows.

Dominik Modest and multi-centre German colleagues, reported that median OS for the FOLFIRI plus cetuximab arm of the German AIO study KRK-0306 (FIRE-3) was 28.7 months vs 25 months for the FOLFIRI plus bevacizumab arm in the intent-to-treatment (ITT) population (p=0.017), while median PFS in the ITT population was 10 vs 10.3 months for the two arms, respectively. When these findings were presented at ASCO earlier this year, authors were challenged to review whether this benefit in OS for the cetuximab arm was in fact due to differences in second line therapies. Data presented here at ESMO 15^th World Congress on Gastrointestinal Cancer show that frequencies of antibody cross-over and continuation beyond progression as well as chemotherapies were balanced in 2nd- line treatment based on current evidence. Differences in 2nd-line treatment are therefore unlikely to explain the observed difference in OS.

Click HERE for slide ‘FIRE-3: 2nd line regimens.
Reproduced from presentation by V.Heinemann at WCGIC 2013.

The overall response rate (ORR)—the primary endpoint of the study – was also comparable between the 2 arms in the ITT analysis although in some 526 patients assessable for response, the ORR was superior in the FOLFIRI plus cetuximab arm at 72 compared with 63 % for the FOLFIRI plus bevacizumab arm (Odds Ratio (OR=1.52; p =0.017). No new safety signals were observed in either arm.

Click HERE for slide ‘FIRE-3: Evaluation of ORR’.
Reproduced from presentation by V.Heinemann at WCGIC 2013.

The study initially enrolled patients independent of KRAS status but was subsequently amended to include only those patients with KRAS WT tumors. A total of 592 patients were randomized to either FOLFIRI every 2 weeks plus cetuximab (400 mg/m² on day 1, followed by 250 mg/m² weekly) or FOLFIRI/bevacizumab (5 mg/kg) every 2 weeks.

Median duration of treatment was 4.8 months in the FOLFIRI plus cetuximab arm compared with 5.3 months in the FOLFIRI plus bevacizumab arm. Median follow-up was 33 months in the FOLFIRI plus cetuximab arm and 39 months in the FOLFIRI plus bevacizumab arm.

Click HERE for slide ‘FIRE-3: Head-to-head study of cetuximab + FOLFIRI vs bevacizumab + FOLFIRI in 1st line mCRC.
Reproduced from presentation by V.Heinemann at WCGIC 2013.