Cetuximab-related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with molecular markers: Results from the German AIO CRC 0104 trial.

Cancers of the Colon and Rectum
Session Type and Session Title: 
General Poster Session C: Cancers of the Colon and Rectum
Abstract Number: 


J Clin Oncol 30, 2012 (suppl 4; abstr 491)
Sebastian Stintzing, Christine Kapaun, Ruediger P. Laubender, Andreas Jung, Jens Neumann, Dominik Paul Modest, Clemens Albrecht Giessen, Nicolas Moosmann, Andreas Wollenberg, Thomas Kirchner, Volker Heinemann; Department of Internal Medicine III, Klinikum Grosshadern, University of Munich, Munich, Germany; Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Munich, Germany; Department of Pathology, University of Munich, Munich, Germany; Department of Dermatology and Allergology, University of Munich, Munich, Germany

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Abstract Disclosures


Background: Skin toxicity is a frequent adverse event of EGFR targeting agents. The role of cetuximab induced skin toxicity (Cet-ST), for the most acneiform skin rash, as a prognostic or a predictive factor of treatment efficacy is currently under discussion. Methods: The prognostic and predictive value of Cet-ST in relation to treatment response and survival of patients of a randomized trial investigating CAPIRI plus cetuximab versus CAPOX plus cetuximab as first-line treatment of mCRC was analyzed. Cet-ST was grouped into clinically relevant (grade 2-3) and non relevant (grade 0-1) toxicity (NCI-CTCAE 3.0). KRAS mutations in codons 12 and 13, EGFR-FISH, EGFR-IHC and EGFR intron-1 polymorphism were evaluated in tumor specimens. Results: A total of 149 patients got cetuximab until the first tumor assessment (6 weeks) and were used for this analysis. Overall response rate was higher in patients with grade 2-3 Cet-ST when compared to grade 0-1 (62.1% vs. 41.3%). Patients without Cet-ST (grade 0) had a short PFS (1.9 months) and OS (11.0 months). PFS (7.8 months vs. 5.2 months) and OS (30.3 months vs. 18.0 months) were longer in patients with Cet-ST grade 2-3 than in patients with grade 0-1 Cet-ST. Almost 90% of Cet-ST occurred during the first two cycles of treatment. When only KRAS codon-12 mutated tumors which are thought not to be sensitive to cetuximab were investigated, Kaplan-Meier differences in PFS and OS times between patients with grade 0-1 Cet-ST and grade 2-3 Cet-ST became statistically significant. In a multivariate analysis, male gender, age and EGFR intron-1 polymorphism were significantly correlated with Cet-ST. Conclusions: Cetuximab related skin toxicity is a strong predictor of outcome. It is proposed that Cet-ST is rather a prognostic than a predictive factor since this effect is most evident in patients with KRAS codon-12 mutated tumors. EGFR intron-1 polymorphism appears to be a predictor of Cet-ST.