Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: The NCIC Clinical Trials Group and AGITG CO.20 trial

Lillian L. Siu, Jeremy D. Shapiro, Derek J. Jonker, Chris S. Karapetis, John R. Zalcberg, John Simes, Felix Couture, Malcolm J. Moore, Timothy J. Price, Jehan Siddiqui, Louise M. Nott, Danielle Charpentier, Winston Liauw, Michael B. Sawyer, Michael Jefford, Nadine M. Magoski, Andrew Haydon, Ian Walters, Jolie Ringash, Dongsheng TuChris J. O'Callaghan

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93 Citations (Scopus)

Abstract

Purpose: The antiepidermal growth factor receptor monoclonal antibody cetuximab has improved survival in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorecta cancer. The addition of brivanib, a tyrosine kinase inhibitor targeting vascular endothelia growth factor receptor and fibroblast growth factor receptor, to cetuximab has shown encouraging early clinical activity Patients and Methods: Patients with metastatic colorectal cancer previously treated with combination chemotherapy were randomly assigned 1:1 to receive cetuximab 400 mg/m2 intravenous loading dose followed by weekly maintenance of 250 mg/m2 plus either brivanib 800 mg orally daily (arm A) or placebo (arm B). The primary end point was overall survival (OS) Results: A total of 750 patients were randomly assigned (376 in arm A and 374 in arm B). Median OS in the intent-to-treat population was 8.8 months in arm A and 8.1 months in arm B (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P =.12). Median progression-free survival (PFS) was 5.0 months in arm A and 3.4 months in arm B (HR, 0.72; 95% CI, 0.62 to 0.84; P <.001). Partia responses observed (13.6% v7.2%; P =.004) were higher in arm A. Incidence of any grade > 3 adverse events was 78% in arm A and 53% in arm B. Fewer patients received ≥ 90% dose-intensity of both cetuximab (57% v 83%) and brivanib/placebo (48% v 87%) in arm A versus arm B, respectively. Conclusion: Despite positive effects on PFS and objective response, cetuximab plus brivanib increased toxicity and did not significantly improve OS in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer.

Original languageEnglish
Pages (from-to)2477-2484
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number19
DOIs
Publication statusPublished - 1 Jul 2013

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