Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).

Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA3506)
Volker Heinemann, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Juergen Lerchenmueller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Joerg Hielscher, Michael Scholz, Sebastian Mueller, Britta Schaefer, Dominik Paul Modest, Andreas Jung, Sebastian Stintzing; Department of Hematology and Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany; Health Center St. Marien GmbH, Amberg, Germany; Onkonet - Onkologie Ravensburg, Ravensburg, Germany; Klinik Herzoghöhe, Bayreuth, Germany; Practice for Medical Oncology, Landshut, Germany; Krankenhaus Nordwest, University Cancer Center, Frankfurt, Germany; Städtisches Klinikum Neuss Lukaskrankenhaus GmbH, Medical Department II, Neuss, Germany; Gemeinschaftspraxis fuer Haematologie und Onkologie, Muenster, Germany; Klinikum Magdeburg, Department for Hematology, Magdeburg, Germany; Onkologische Schwerpunktpraxis, Bad Soden, Germany; Klinikum Weiden, Weiden, Germany; Onkologische Schwerpunktpraxis Kronach, Kronach, Germany; Medical University of Vienna, Vienna, Austria; Klinikum Chemnitz gGmbH, Klinik fuer Allgemein- und Viszeralchirurgie, Chemnitz, Germany; Klinikum Stuttgart, Innere Medizin, Stuttgart, Germany; Ambulantes Onkologie Centrum, Ansbach, Germany; Westpfalz-Klinikum GmbH, Klinik fuer Innere Medizin I, Kaiserslautern, Germany; Department of Pathology, Ludwig-Maximilians University of Munich, Munich, Germany

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Abstract Disclosures


Background: In patients (pts) with KRAS, wild-type metastatic colorectal cancer (mCRC) a head to head comparison of anti-EGFR- and anti-VEGF-directed first-line therapy has not been reported with regard to the FOLFIRI backbone. The AIO KRK-0306 study was therefore designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC pts not pretreated for metastatic disease. Methods: Pts were randomized to FOLFIRI (Tournigand regimen) every two wks plus cetuximab (400 mg/m² day 1, followed by 250 mg/m² wkly = arm A) or bevacizumab (5 mg/kg every two wks = arm B). The intent-to-treat (ITT) population comprised all pts who had at least completed one application of therapy. While recruitment initially was independent of KRAS status, an amendment confined inclusion to KRAS wildtype (WT) tumors. Recruitment was completed in October 2012. The primary study endpoint was objective response rate (ORR, investigators read). Results: Among 735 pts of the ITT-population, KRAS-WT was identified in 592. Of these, 297 pts were randomized to arm A and 295 to arm B. Median age was 64 years, 66% of pts were male, and ECOG PS 0-1 was observed in 98% of pts. Median duration of treatment was 4.7 mo vs 5.3 mo, respectively. While in the ITT analysis, ORR was comparable in arms A vs B (62% vs 57%, odds ratio 1.249), a significant superiority was found for assessable pts in arm A. Median PFS of the ITT population was nearly identical (10.3 vs 10.4 mo, HR 1.04, p=0.69), however, overall survival (OS) showed a significantly better outcome in arm A vs arm B (28.8 vs 25.0 mo, HR 0.77, p=0.0164, 95% CI: 0.620-0.953). Sixty-day mortality was low in both arms (1.01% vs 2.71%). Conclusions: ORR was comparable between arms in the ITT analysis, but favored arm A in assessable pts. Significantly superior OS was observed in KRAS-WT patients receiving cetuximab plus FOLFIRI as first-line treatment. Clinical trial information: NCT00433927.