FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (mCRC): Analysis of patients with KRAS-mutated tumors in the randomized German AIO study KRK-0306.

3575 Background: The German AIO study KRK-0306 is a randomized phase III trial that investigates the efficacy and safety of cetuximab plus FOLFIRI versus bevacizumab plus FOLFIRI in the first-line treatment of mCRC. Until September 2008, patients (pts) without knowledge of their KRAS mutational status had been enrolled. Here, results of the subgroup of pts with mCRC carrying a mutated KRAS gene are presented. METHODS Until September 2008, a total of 336 mCRC pts were randomized to FOLFIRI (irinotecan 180mg/m2, folinic acid 400mg/m2, 5-FU 400mg/m2 bolus application, day 1 followed by continuous infusion of 2,400mg/m2 5-FU over 46h q2w) plus cetuximab (400mg/m2 day 1, followed by 250mg/m2 weekly = arm A) or bevacizumab (5mg/kg q2w = arm B). At the time of analysis, KRAS mutation was documented in 96 pts (ITT population). The primary endpoint of this study was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), rate of secondary liver resections, toxicity and safety. RESULTS Median follow-up was 20.4 months. In pts assessable for treatment efficacy (on treatment until the first tumor assessment) receiving arm A (n=41) versus arm B (n=46), ORR was 43.9% versus 47.8%. In the ITT population PFS was 7.5 months versus 8.9 months, and OS (56% of events occurred) was 21.1 months versus 16.8 months, respectively, indicating no significant differences between the two treatment arms (HR 1.12). A total of 8 pts (8.3%) reached surgical resectability for metastases. The most common grade 3/4 toxicities (arm A versus arm B) were exanthema (20% versus 0%), hypertension (8% versus 21.7%) and thromboembolic events (10% versus 19.5%). In arm A skin rash grade 1-4 was associated with a trend towards longer PFS (7.6 versus 3.5 months, logrank p=0.108). 60-day mortality rate was 1%. CONCLUSIONS In this analysis of KRAS mutated pts, no significant differences with regard to efficacy could be observed between pts receiving chemotherapy plus cetuximab versus bevacizumab.