OBJECTIVES : Uncertainty exists regarding comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC), due to conflicting efficacy evidence of previous randomised clinical trials and the absence of Quality of Life (HRQoL) studies. We conducted a mainly retrospective head-to-head multi-cohort study comparing clinical outcomes from both antibodies, in which was nested a smaller prospective cohort study for measuring patient-reported outcomes (PROs).

METHODS : Retrospective cohorts were defined by treatment line, and subgroups by (K)RAS status and tumour sidedness. Among other effectiveness outcomes, we compared response rates, progression-free (PFS) and overall survival (OS). PROs were measured prospectively through EORTC disease-specific instruments. Methods and reporting followed STROBE guidelines and SISAQOL / SPIRIT-PRO recommendations.

RESULTS : Between 2010 and 2018, 311 patients were included in overall analysis. 44 were further allocated to PROs nested cohorts. Except for (K)RAS mutation status, baseline characteristics were balanced across groups. In full analyses, PFS (first-line: HR=0.85; P=0.26; second-line: HR=1.16; P=0.51) and OS (first-line: HR=0.83; P=0.26; second-line: HR=0.88; P=0.58) were similar between treatment arms. In subgroup analyses (first-line), we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR=0.52; P=0.025; OS: HR=0.60; P=0.11), but not in left-sided or (K)RAS wild-type tumours. Response rates were higher for bevacizumab in patients bearing right-sided primaries and similar across other comparisons. During initial 12 weeks of treatment, a higher proportion of patients in cetuximab arm experienced clinically meaningful (≥10%) deterioration of HRQoL: 53.8% vs 18.2% at 6 weeks and 66.7% vs 12.5% at 12 weeks. We also observed increased scoring on symptom scales in cetuximab cohort.

CONCLUSIONS : This study provides evidence suggesting bevacizumab and cetuximab-containing regimens result in similar clinical effectiveness outcomes in mCRC, except for right-sided tumours, where bevacizumab performed better. Cetuximab led to a progressive negative impact on HRQoL, when compared to baseline and bevacizumab. These findings should be further explored through randomised studies.