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Whether bevacizumab or anti\u2010epidermal growth factor receptor (anti\u2010EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first\u2010line treatment for inoperable <jats:italic>KRAS<\/jats:italic> wild\u2010type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti\u2010EGFR mAb needs to be addressed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established a cohort of patients with <jats:italic>KRAS<\/jats:italic> wild\u2010type mCRC who were treated with first\u2010line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 6482 patients were included; bevacizumab and anti\u2010EGFR mAb were the first\u2010line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti\u2010EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.012) and time to treatment failure (TTF; median, 11.3 vs. 10\u2009months, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Among left\u2010sided primary tumors, the OS and TTF benefits of anti\u2010EGFR mAb remained. Among right\u2010sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first\u2010line anti\u2010EGFR mAb therapy remained an independent predictor of longer OS and TTF for left\u2010sided primary tumors. Patients who received anti\u2010EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) than patients who received bevacizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>For patients who received first\u2010line doublet chemotherapy for <jats:italic>KRAS<\/jats:italic> wild\u2010type mCRC, adding anti\u2010EGFR mAb was associated with significantly longer OS and TTF, especially for left\u2010sided primary tumors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6196","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T08:46:32Z","timestamp":1686905192000},"page":"15176-15186","source":"Crossref","is-referenced-by-count":6,"title":["Treatment outcome comparisons of <scp>first\u2010line<\/scp> targeted therapy in patients with <scp><i>KRAS<\/i> wild\u2010type<\/scp> metastatic colorectal cancer: A nationwide database 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