Cetuximab plus FOLFIRI first line in patients (pts) with metastatic colorectal cancer (mCRC): A quality-of-life (QoL) analysis of the CRYSTAL trial

Abstract

4076 Background: Assessing QoL is important to evaluate the impact of treatment on pts with mCRC. The phase III CRYSTAL trial compared cetuximab plus FOLFIRI with FOLFIRI alone in the first-line treatment of patients with EGFR-expressing mCRC. Primary endpoint was progression-free survival (PFS); QoL was a secondary endpoint. Methods: Pts were randomised 1:1 to cetuximab (400 mg/m2 initial dose then 250 mg/m2/wk) plus FOLFIRI q2w (irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2400 mg/m2 over 46 h) (Group A, n=599) or FOLFIRI alone (Group B, n=599). QoL was assessed with the EORTC QLQ-C30 (v3.0) questionnaire. Pts were to complete the questionnaire at baseline, every 4 cycles, and at final tumor assessment. The primary QoL analysis focused on Global Health Status and Social Functioning scales and employed a pattern-mixture model that included the drop-out pattern. Descriptive statistics were provided for each multi-item scale considering QoL changes over time. Results: Risk of disease progression was significantly reduced by 15% (HR=0.85) in favor of Group A (p=0.0479); pts with KRAS wild-type (wt) tumors in Group A had a 32% (HR=0.68) reduced risk of progressing. Questionnaire completion compliance rates were similar between treatment groups. Pattern-mixture analyses showed no statistically significant differences between the two treatment groups for changes from baseline on the Global Health Status (p=0.29) and Social Functioning (p=0.39) scales. Comparing treatment groups in terms of QoL scores over time resulted in no statistically significant differences, apart from nausea/vomiting in favor of the cetuximab group at week 16 (10.2 vs 13.3; p=0.0129), week 32 (9.3 vs 12.5; p=0.0488) and week 40 (7.6 vs 12.5; p=0.0194). Conclusions: In pts with mCRC, cetuximab plus FOLFIRI first-line significantly prolongs PFS compared with FOLFIRI alone while preserving QoL. The PFS benefit is even more pronounced for pts with KRAS wt tumors. The EORTC QLQ-C30 Social Functioning scale was expected to reflect skin reactions related to cetuximab, but there was neither a clinically meaningful nor statistically significant difference between groups. [Table: see text]