1081PBenefit of cetuximab addition to a platinum-fluorouracil-based chemotherapy in an unselected population of metastatic head and neck cancer patients and effect of KRAS Lcs6 variation on cetuximab response

Background: While the EXTREME protocol, including platinum (P) fluorouracil (FU) and cetuximab (Cx), is the gold-standard first line chemotherapy for metastatic head neck cancer patients (MHNC), its benefit in an unselected population has never been evaluated. Furthermore, KRAS Lcs6 variation was reported as a potential marker for greater efficacy of EGFR-targeted therapy. We investigated the benefit on progression-free survival (PFS) and overall survival (OS) of adding Cx to PFU as first line treatment for MHNC in an unselected population. We also assessed if there was a differential efficacy of Cx according to KRAS Lcs6 status. Methods: This monocentric retrospective study included all the patients treated by at least two cycles of PFU+/-Cx between 2005 and 2014 as first line of palliative chemotherapy for MHNC. When tumor samples were available, the KRAS LCS6 variant status (rs61764370) was determined by pyrosequencing, and the p16 status by immuno-histo-chemistry. Results: 134 patients were included: 59 (44%) treated with PFU and 75 (56%) with PFUCx. Baseline characteristics were comparable between the two groups. Of note 30% of the patients had a stage 2 or 3 performance status (PS). In univariate analysis, a longer median PFS was observed with PFUCx compared to PFU (6.1 vs 4.4 months respectively, HR 0.68, p = 0.02). Median OS were not different (11.1 months with PFUCx versus 9.1 with PFU, p = 0.2). Among the 110 tumor samples available, 29 (25%) had a KRAS-variant and 14 (12.7%) were p16 positive. No differences in OS nor PFS were observed according to the KRAS-variant status. When considering only the patients treated with PFUCx, presence of the KRAS-variant (n = 17) was not associated with a better response (p = 0.5). In a multivariate analysis including PS ≤ 1, addition of Cx, KRAS status, p16 status and age ≤ 55 as variables; addition of Cx to PFU was the only factor related to a better PFS (p = 0.008). Conclusions: This retrospective study confirmed the effectiveness of the EXTREME protocol on PFS in an unselected population of MHNC patients. KRAS LCS6 variant was not related to a differential response to Cetuximab in MHNC population. Legal entity responsible for the study: Centre Henri Becquerel Funding: IRON - Centre Henri Becquerel Disclosure: All authors have declared no conflicts of interest.