Background: AIO KRK0306 (FIRE 3) trial compared first-line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients with KRAS exon 2 wild-type metastatic colorectal cancer (mCRC). We investigated choice and duration of second-line therapies, as well as overall survival (OS) and OS from beginning of second-line therapy according to second-line treatment. Methods: The protocol recommended second-line therapy with FOLFOX plus bevacizumab vs. irinotecan plus cetuximab in arm A vs. B, but physician were free to choose any regimen. second-line treatment was defined as any new anticancer drug for mCRC following first-line therapy. Duration of second-line therapy was calculated as time from first to last application of second-line treatment. Results: There were 260/297 patients in arm A and 250/295 patients in arm B who were alive after first-line therapy. Of those, 78.5% of patients arm A and 76.4% in arm B received second-line therapy so far. First-line progression free survival (PFS) according to second-line antibody use was associated with 9.2 (anti-vascular endothelial growth factor [VEGF]), comparing to 9.7 (anti-epidermal growth factor receptor [EGFR]) and 11.3 months (no mAB); p=0.001. Correspondingly, OS was 25.2 (anti-VEGF) vs. 23.7 (anti-EGFR) vs. 30.8 months (no mAB), p=0.02. First-line PFS according to seconnd-line oxaliplatin (Ox) use was associated with 9.9 (Ox), comparing to 9.9 months (no Ox); p=0.56. OS according to Ox-use was 27.1 (ox) vs. 29.1 months (no Ox); p=0.10. 2nd-line therapy was administered for a median of 17.2 weeks in arm A and 14.0 weeks in arm b (p=0.08). Second-line regimens with antibody-crossover were administered for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p=0.06). Updated results might be presented at the annual meeting. Conclusions: This retrospective analysis indicates that second-line application of antibodies was favoured in patients with shorter first-line PFS, suggesting that preplanned second-line therapy may not reflect therapeutic reality. Correspondingly, second-line treatment without antibodies compared to antibody-based regimens was associated with longer OS. A trend towards longer second-line therapy was observed in favour of patients receiving cetuximab as first-line therapy. Clinical trial information: NCT00433927.