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

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. 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/m(2) loading dose, then 250 mg/m(2)/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). 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. 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. (C) 2014 Published by Elsevier Ltd.