The relationship between the development of rash and clinical and quality of life outcomes by Kras mutation status in patients with colorectal cancer treated with cetuximab in NCIC CTG CO.17.

Abstract

481 Background: The NCIC Clinical Trials Group CO.17 trial, conducted with the Australasian Gastrointestinal Trials Group, showed cetuximab monotherapy (CET vs. best supportive care [BSC]) improved overall (OS) and progression-free survival (PFS) and maintained quality of life (QoL) in patients previously treated for advanced colorectal cancer. Correlative analyses showed strong relationships between CET benefits and both rash development and Kras mutation status. Association between rash and CET benefits is now presented by Kras mutation status. Methods: Rash was graded weekly by NCI CTC 2.0 criteria. Landmark-type analyses (LTA) were performed by excluding patients who died within 28 days and then grouping by rash severity (gr 2+ vs. gr 0/1) based both on worst grade ever developed (LTA1) and worst grade on or before day 28 (LTA2). Multivariate Cox models were conducted separately for wild-type (WT) and mutated (MUT) Kras tumors. Results: More rash of severity gr 2+ was observed in WT than MUT patients treated with CET (57.3% vs. 44.4%; p = 0.08). The median OS, PFS, and HRs from LTA2 are presented for WT and MUT groups (see Table). Conclusions: Rash severity was positively correlated with PFS and OS in Kras WT patients who received CET, although only for gr 2+ rash did OS significantly exceed that of BSC patients. In Kras MUT patients, neither gr 0/1 nor gr 2+ rash was associated with either improved PFS or OS vs. BSC patients. Quality of life outcomes will also be reported by Kras mutation status. [Table: see text] [Table: see text]