Annals of Oncology Advance Access originally published online on May 22, 2009
Annals of Oncology 2009 20(8):1375-1382; doi:10.1093/annonc/mdp011
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gastrointestinal tumors |
Radiological tumor size decrease at week 6 is a potent predictor of outcome in chemorefractory metastatic colorectal cancer treated with cetuximab (BOND trial)
1 Service de Gastro-entérologie, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels
2 International Drug Development Institute, Louvain-la-Neuve, Belgium and Center for Statistics, Universiteit Hasselt, Diepenbeek
3 Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium
4 Merck KGaA, Darmstadt, Germany
* Correspondence to: Prof. S. Tejpar, Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Tel: +32-16-34 42 18; Fax: +32-16-34 44 19; E-mail: sabine.tejpar{at}uz.kuleuven.ac.be
Background: Early radiological tumor shrinkage may be associated with better long-term outcome in chemorefractory metastatic colorectal cancer (cmCRC) treated with cetuximab. We aimed at validating this in a large and independent series.
Patients and methods: Of the 329 patients, 289 had a measurement both at baseline and week 6. Tumor shrinkage was expressed as a relative decrease compared with baseline and categorized according to a previously reported cut-off value (
10%) or used as a continuous variable.
Results: Median time to progression (TTP) was 6.1 [95% confidence interval (CI) 5.1–7.2] versus 1.5 months (95% CI 1.4–1.7) in patients with [99 patients (34.3%)] or without [190 patients (65.7%)] tumor shrinkage, respectively, at week 6 [hazard ratio (HR) 0.23 (95% CI 0.17–0.32)]. The median overall survival (OS) was 13.7 (CI NA) versus 6.9 months (95% CI 6.1–7.7) [HR 0.21 (95% CI 0.14–0.32)], respectively. In a multivariate model, early tumor decrease outperformed skin toxicity as a predictor of long-term outcome.
Conclusions: Tumor shrinkage at 6 weeks is a strong predictor of TTP and OS in cmCRC patients treated with cetuximab with or without irinotecan. This suggests early tumor shrinkage is the hallmark of efficacy of cetuximab and reliably identifies the subpopulation that is sensitive to the drug. Early tumor shrinkage can be used as a marker of efficacy in clinical practice, as such or in combination.
Key words: cetuximab, metastatic colorectal cancer, tumor measurements
Received for publication October 20, 2008. Revision received December 25, 2008. Accepted for publication January 8, 2009.