A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

Hickish, T. et al. (2014) A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer. European Journal of Cancer, 50(18), pp. 3136-3144. (doi: 10.1016/j.ejca.2014.08.008) (PMID:25441408)

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Purpose: This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated.<p></p> Patients and methods: Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines. All patients with KRAS-mutated tumours received afatinib. Primary end-points were objective response (OR) for the wild-type group and disease control for the KRAS-mutated group. Secondary end-points were progression-free survival (PFS) and overall survival (OS).<p></p> Results: Patients with KRAS wild-type tumours (n = 50) received afatinib (n = 36) or cetuximab (n = 14). Unconfirmed and confirmed ORs were 3% and 0% for afatinib versus 20% and 13% for cetuximab (odds ratio: 0.122 [P = 0.0735] and <0.001, respectively). Median PFS was 46.0 and 144.5 days for afatinib and cetuximab, respectively. Median OS was 355 days with afatinib but not reached for cetuximab. In the KRAS-mutated group (n = 41), five (12%) patients achieved confirmed disease control (stable disease; P = 0.6394 [comparison versus 10%]); no ORs were reported. Median PFS and OS were 41.0 and 173 days, respectively. Most frequent treatment-related adverse events were diarrhoea and rash across groups.<p></p> Conclusions: The efficacy of afatinib was inferior to cetuximab in patients with KRAS wild-type mCRC. In patients with KRAS-mutated tumours, disease control was modest with afatinib. Afatinib had a manageable safety profile.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cassidy, Professor James and MacPherson, Professor Iain
Authors: Hickish, T., Cassidy, J., Propper, D., Chau, I., Falk, S., Ford, H., Iveson, T., Braun, M., Potter, V., Macpherson, I. R., Finnigan, H., Lee, C., Jones, H., and Harrison, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:European Journal of Cancer
Publisher:Elsevier Ltd.
ISSN (Online):1879-0852

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