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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.
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.
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.
Shares Irinotecan (and liposomal irinotecan), VEGF / VEGFR, Roche / Genentech, Fluorouracil (5-FU).
Shares Irinotecan (and liposomal irinotecan), VEGF / VEGFR, Fluorouracil (5-FU), Bevacizumab.
Shares Irinotecan (and liposomal irinotecan), Fluorouracil (5-FU), Colorectal cancer.
Shares Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL), 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, Colorectal cancer.
Shares Irinotecan (and liposomal irinotecan), Fluorouracil (5-FU), Colorectal cancer.
Shares VEGF / VEGFR, Bevacizumab, Colorectal cancer.
Shares Fluorouracil (5-FU), Bevacizumab, Colorectal cancer.
Shares Irinotecan (and liposomal irinotecan), VEGF / VEGFR, Fluorouracil (5-FU), Bevacizumab.