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Liu, Lian; Erickson, Nicole Tonya; Ricard, Ingrid; Weikersthal, Ludwig Fischer von; Lerch, Markus M.; Decker, Thomas; Kiani, Alexander; Kaiser, Florian; Heintges, Tobias; Kahl, Christoph; Kullmann, Frank; Scheithauer, Werner; Link, Hartmut; Hoeffkes, Heinz-Gert; Moehler, Markus; Gesenhues, Alena Britta; Theurich, Sebastian; Michl, Marlies; Modest, Dominik P.; Alguel, Hana; Stintzing, Sebastian; Heinemann, Volker and Holch, Julian W. (2021): Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306). In: International Journal of Cancer, Vol. 150, No. 1: pp. 112-123

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Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE-3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS-WT tumors (ie, wild-type in KRAS and NRAS exons 2-4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL >= 5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months;hazard ratio [HR]: 1.64;95% confidence interval [CI] = 1.13-2.38;P = .0098) and progression-free survival (11.8 vs 9.0 months;HR: 1.72;95% CI = 1.18-2.5;P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.

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