{"entity":{"id":"paper-hurwitz-bevacizumab-crc-nejm-2004","kind":"paper","name":"Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life","aka":[],"tldr":"Adding the VEGF antibody bevacizumab to irinotecan-based chemotherapy prolonged survival in first-line metastatic colorectal cancer, the first time blocking a tumour's blood supply had been shown to help patients.","summary":"This phase 3 trial randomised 813 patients with untreated metastatic colorectal cancer to irinotecan, fluorouracil and leucovorin (IFL) plus bevacizumab or IFL plus placebo. Bevacizumab improved overall survival, progression-free survival and response rate. Grade 3 hypertension was more common with bevacizumab but manageable, and gastrointestinal perforation appeared as a rare but serious class effect. The trial led to the first approval of an anti-angiogenic drug and validated Judah Folkman's decades-old hypothesis that tumours depend on new blood vessels.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa032691"}],"tags":[],"related":["colorectal-roadmap","paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["vegf"],"drugs":["bevacizumab","irinotecan","fluorouracil"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032691","authors":"Hurwitz H, Fehrenbacher L, Novotny W, et al.","paperType":"rct","findings":["813 patients with untreated metastatic colorectal cancer; IFL plus bevacizumab or placebo.","Median overall survival 20.3 vs 15.6 months, hazard ratio 0.66.","Median progression-free survival 10.6 vs 6.2 months, hazard ratio 0.54; response rate 44.8% vs 34.8%.","Grade 3 hypertension 11.0% vs 2.3%; gastrointestinal perforation in 1.5% of bevacizumab patients."],"whatItMeans":"This trial opened anti-angiogenic therapy as a class, and bevacizumab went on to approvals in lung, kidney, ovarian, cervical and brain cancers. It also set the pattern of modest but real survival gains from adding a biologic to chemotherapy, and introduced hypertension, proteinuria and perforation as the signature side effects clinicians now monitor.","caveats":["IFL is no longer a standard backbone; FOLFOX and FOLFIRI replaced it.","Benefit in later trials was smaller and no predictive biomarker for bevacizumab has emerged.","Placebo-controlled but with an active chemotherapy backbone in both arms."],"changedPractice":true,"participants":813},"route":"/key-papers/paper-hurwitz-bevacizumab-crc-nejm-2004/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}],"paper":[{"id":"paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","kind":"paper","name":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)","route":"/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"target":[{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}]}}