Objective:

There is limited scientific evidence on the cetuximab exposure- response relationship and no concentration threshold has been associated with optimal disease control. The aims were to assess, in a real-life setting, the relationship between steady state cetuximab concentrations (Ctrough, SS) and disease control.

Method:

A prospective observational study in patients with metastatic colorectal cancer or head and neck cancer treated with cetuximab. Steady state trough concentrations were compared with the results of radiological assessment of response (progression or clinical benefit). Generalized estimating equations analysis was performed. To test the association between steady state concentrations and overall survival and progression-free survival, Cox proportional hazard models were developed. An optimal cut-off point was searched using the area under the receiver operating characteristic curve.

Results:

A total of 30 steady state cetuximab concentrations from 16 patients were analysed. Median Ctrough, SS was 26.86 mg/L and there was marked inter- and intraindividual variability (standard deviation 32.4 mg/L and 16.9 mg/L, respectively). A positive association was found between cetuximab Ctrough, SS and clinical benefit (odds ratio 1.24, 95% confidence interval: 0.95-1.63, . = 0.113), although without reaching statistical significance. The area under the receiver operating characteristic curve (. = 30) had moderate discrimination power (0.71; 95% confidence interval 0.49‑0.93), and the empirical optimal cutoff point was 19.12 mg/L. However, no association was observed between cetuximab Ctrough, SS and survival in metastatic colorectal cancer or neck cancer patients.

Conclusions:

We cannot confirm a relationship between cetuximab Ctrough, SS and disease control despite a positive association. This study was conducted with a small sample, which reduces the power analysis. Further controlled randomised studies with a sufficient number of patients are needed.