Pretreatment and postresection epidermal growth factor receptor (EGFR) pathway mutations in a prospective phase II trial (EXCITE) of preoperative cetuximab-containing chemoradiation (CRT) in locally advanced rectal cancer (LARC).

458 Background: Little data exists comparing pre- and post-CRT EGFR pathway mutations in LARC. Methods: Patients had MRI-defined LARC threatening or involving the surgical resection margin. CRT used pelvic radiotherapy (RT) 45Gy in 25 daily fractions with concurrent capecitabine (650mg/m2 bid PO 5 days/week), IV cetuximab (400mg/m2 one week prior then weekly at 250mg/m2 weeks 1-5) and IV irinotecan (weekly at 60mg/m2weeks 1-4). Surgery was 8 weeks after CRT. EGFR pathway mutations were not assessed prospectively. After study completion DNA was extracted from pre-treatment biopsies and post-resection specimens by macrodissecting areas of greatest tumour cell density. KRAS codons 12, 13, 61, 146, NRAS codons 12, 13, 61, PIK3CA codons 542, 545, 546, 1047 and the BRAF V600E hotspot were then pyrosequenced. Results: From 04/09-10/11, 80 patients commenced RT. 76 patients had surgery, with pathological complete response (CR) in 14 (18%) and near-complete (microfoci) in 6 (8%). Four patients had no surgery due t...