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

Abstract

4130 Background: The National Cancer Institute of Canada Clinical Trials Group CO.17 trial, conducted in collaboration with the Australasian Gastrointestinal Trials Group, demonstrated cetuximab monotherapy (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 that expressed the Epidermal Growth Factor Receptor (EGFR). We analyzed the correlation between the occurrence of rash and clinical and QoL outcomes in CO.17 patients who received cetuximab therapy. Methods: Rash was graded weekly according to NCI CTC version 2.0 criteria. In the principle analysis, patients were classified into the “no rash” group until rash of any grade developed (= entered “rash” group). A Cox model with rash as a dichotomous time-dependent covariate (CMTDC) was used to compare clinical and QoL outcomes between these two groups. Two additional exploratory landmark-type analyses (LTA) were also performed by first excluding all patients who died within 28 days of randomization, and then classifying patients according to severity of rash (grade 0, 1, 2+) based on 1) the worst grade of rash ever developed (LTA1) and 2) the worst grade of rash on or before day 28 of the study (LTA2). These three groups were compared in Cox models as fixed covariates. Results: In patients who received cetuximab and experienced rash, the median time to onset of rash was 10 days and 90% experienced rash within 29 days. The hazard ratio (HR) of OS between the “rash” and “no rash” groups estimated from CMTDC was 0.58 (95% CI: 0.38–0.87; p=0.009). The median OS and corresponding HR from two landmark- type analyses are presented in the table below. Results for other clinical outcomes and QoL will be presented. Conclusions: All analyses demonstrated a strong correlation between rash development and clinical benefit in colorectal patients treated with cetuximab. Median Overall Survival Worst ever grade of rash (LTA1) Worst grade of rash by day 28 (LTA2) Grade 0 2.6 months 4.3 months Grade 1 4.8 months 4.6 months Grade 2+ 8.4 months 9.1 months HR: Grade 2+ vs Grade 0 0.33 (95% CI 0.22–0.50; p<0.001) 0.52 (95% CI: 0.37, 0.74; p=0.0002) HR: Grade 2+ vs Grade 1 0.54 (95% CI: 0.41–0.72; p<0.0001) 0.53 (95% CI: 0.39–0.72; p<0.0001) No significant financial relationships to disclose.