• Dominik P Modest, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Svantje Held, Markus Möhler, Andreas Jung, Thomas Kirchner, and Volker Heinemann.
• Dominik P. Modest, Sebastian Stintzing, and Volker Heinemann, University Hospital Grosshadern; Andreas Jung and Thomas Kirchner, University of Munich, Munich; Dominik P. Modest, Sebastian Stintzing, Volker Heinemann, Andreas Jung, and Thomas Kirchner, German Cancer Consortium and German Cancer Research Centre, Heidelberg; Ludwig Fischer von Weikersthal, Gesundheitszentrum St Marien, Amberg; Thomas Decker, Oncological Practice, Ravensburg; Alexander Kiani, Klinikum Bayreuth, Bayreuth; Ursula Vehling-Kaiser, Oncological Practice, Landshut; Salah-Eddin Al-Batran, Krankenhaus Nordwest, Frankfurt am Main; Tobias Heintges, Städtisches Klinikum Neuss, Neuss; Christian Lerchenmüller, Oncological Practice, Münster; Christoph Kahl, Staedtisches Klinikum Magdeburg, Magdeburg; Gernot Seipelt, Oncological Practice, Bad Soden; Frank Kullmann, Klinikum Weiden, Weiden; Martina Stauch, Oncological Practice, Kronach; Svantje Held, ClinAssess, Leverkusen; Markus Möhler, Johannes-Gutenberg Universität and German Cancer Consortium, Mainz, Germany; and Werner Scheithauer, Medical University Vienna, Vienna, Austria.
• J. Clin. Oncol. 2015 Nov 10; 33 (32): 3718-26.

PurposeWe investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer.Patients And MethodsStart of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3.ResultsOf 592 patients in the intent-to-treat population, 414 (69.9%) received second-line and 256 (43.2%) received third-line therapy. In subsequent treatment lines, 47.1% of patients originally assigned to arm A received bevacizumab, and 52.2% originally assigned to arm B received either cetuximab or panitumumab. Oxaliplatin was subsequently used in 55.9% (arm A) and 53.2% (arm B) of patients. Second-line therapy was administered for a median duration of 5.0 versus 3.2 months (P < .001) in study arm A versus B. Progression-free (6.5 v 4.7 months; hazard ratio, 0.68; 95% CI, 0.54 to 0.85; P < .001) and overall survival (16.3 v 13.2 months; hazard ratio, 0.70; 95% CI, 0.55 to 0.88; P = .0021) from start of second-line therapy were longer in patients in arm A compared with arm B.ConclusionOur data suggest that the sequence of drug application might be more important than exposure to single agents. In patients with RAS wild-type tumors, first-line application of anti-epidermal growth factor receptor-directed therapy may represent a favorable condition for promoting effective subsequent therapy including antiangiogenic agents.© 2015 by American Society of Clinical Oncology.

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