{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T20:13:00Z","timestamp":1776888780124,"version":"3.51.2"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Three vascular endothelial growth factor (VEGF) inhibitors, Bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are widely used for metastatic colorectal cancer (mCRC) patients who are treated with second\u2010line chemotherapy. The difference in outcome between the three drugs has not been evaluated. In contrast to epidermal growth factor receptor inhibitors, VEGF inhibitors have few candidate predictors of efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Consecutive mCRC patients who were treated with second\u2010line chemotherapy were retrospectively enrolled. Overall response rate (ORR), progression\u2010free survival (PFS), overall survival (OS), and safety were assessed. Subgroup analyses of prognostic and predictive efficacy markers were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 119 (41.2%), 107 (37.0%), and 63 patients (21.8%) were treated with FOLFIRI +BEV, RAM, or AFL, respectively. ORR, PFS, and OS showed no significant differences between three groups. However, the frequency of grade 3 or 4 adverse events (AEs) in the FOLFIRI +AFL group was significantly higher than that in the other groups (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Patients with grade 3 or 4 AEs, especially hypertension and neutropenia within the first four cycles of treatment had significantly longer PFS and OS than those without AEs, irrespective of treatment with VEGF inhibitors (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). PFS in patients without prior BEV exposure was also significantly longer than that in patients with prior BEV exposure (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chemotherapeutic efficacy did not differ between the groups. Grade 3 or 4 AEs within the first four cycles of treatment and prior BEV exposure may be an effective predictor of treatment efficacy in mCRC patients administered VEGF inhibitors as second\u2010line chemotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3638","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T13:15:34Z","timestamp":1608642934000},"page":"615-625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Early hypertension and neutropenia are predictors of treatment efficacy in metastatic colorectal cancer patients administered FOLFIRI and vascular endothelial growth factor inhibitors as second\u2010line chemotherapy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4742-0446","authenticated-orcid":false,"given":"Hiroki","family":"Osumi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Cancer Institute 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