Clonal evolution and KRAS-MET coamplification during secondary resistance to EGFR-targeted therapy in metastatic colorectal cancer

We report the clinical and molecular characteristics of a 69-year-old woman with metastatic colorectal cancer, treated with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody panitumumab, displaying peculiar molecular tumour heterogeneity at progression consisting of KRAS and MET amplification as distinct drivers associated with acquired resistance.The patient had rectosigmoid junction adenocarcinoma, G3, KRAS (exon 2) wild type, pT3N2(5/14)M0 treated with surgery in March 2007 and then adjuvant capecitabine (Xeloda) and oxaliplatin (XELOX) chemotherapy. In April 2009 the patient had pelvic relapse and underwent presacral, paraortic and inferior mesenteric lymphadenectomy confirming metastatic colon adenocarcinoma, KRAS (exon 2), BRAF and PIK3CA wild type, human epidermal growth factor receptor 2 (HER2) 2+ without amplification by in situ hybridisation1 and no amplification of KRAS or MET . The patient received subsequent chemotherapy for stage IV disease with XELOX with progression and subsequently FOLFIRI. At disease progression, based on the RAS wild type status, on August 2010 the patient started treatment with panitumumab, achieving partial response which was maintained for 1 year. At that …