Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life
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.
Overview
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.
- 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.
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.
- 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.
Similar pages
not linked directly; found by shared links- TrialSUNLIGHT
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