# Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life

Source: https://onco.cc/key-papers/paper-hurwitz-bevacizumab-crc-nejm-2004/  
OnCo record `paper-hurwitz-bevacizumab-crc-nejm-2004` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2004
- DOI: 10.1056/NEJMoa032691
- Authors: Hurwitz H, Fehrenbacher L, Novotny W, et al.
- 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.
- What it means: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa032691

## Connected records

- roadmaps: [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](https://onco.cc/roadmaps/colorectal-roadmap/)
- key papers: [Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)](https://onco.cc/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- targets: [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)

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