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Prospective study of EGFR intron 1 (CA)n repeats variants as predictors of benefit from cetuximab and irinotecan in chemo-refractory metastatic colorectal cancer (mCRC) patients

The Pharmacogenomics Journal volume 14, pages 322–327 (2014)Cite this article

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Abstract

The number of CA tandem repeats (CA)n in a highly polymorphic region of EGFR (epidermal growth factor receptor) intron 1 may affect gene transcription; the potential impact of allelic variants on the efficacy of cetuximab in metastatic colorectal cancer (mCRC) patients is debated for long. This study aimed at prospectively estimating the impact of EGFR intron 1 (CA)n variants on clinical outcome in KRAS exon 2 and BRAF wild-type chemo-refractory mCRC patients, receiving cetuximab and irinotecan. Variants presenting⩾20 CA repeats were defined as short (S) and long (L), respectively. One hundred and fifteen patients were included. No differences in progression-free survival or overall survival were observed between L- and SS genotypes (hazard ratio (HR)=1.00 (95% confidence interval (CI): 0.67–1.50), P=0.991; HR=1.32 (95% CI: 0.81–2.16), P=0.261). Exploratory analyses adopting other cutoff values previously described led to similar results. This prospective study did not confirm any previous retrospective finding, reporting a predictive or prognostic effect of EGFR (CA)n repeats allelic variants in chemo-refractory mCRC patients receiving cetuximab and irinotecan.

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Author notes

  1. F Loupakis, C Antoniotti and C Cremolini: These authors contributed equally to this work.

Authors and Affiliations

  1. U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy

    F Loupakis, C Antoniotti, C Cremolini, M Schirripa, L Salvatore, G Masi, F Marmorino & A Falcone

  2. Istituto Toscano Tumori (ITT), Firenze, Italy

    F Loupakis, C Antoniotti, C Cremolini, M Schirripa, L Salvatore, G Masi, F Marmorino & A Falcone

  3. Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA

    W Zhang, D Yang, T Wakatsuki, P Bohanes, L Benhaim, Y Ning, R El-Khoueiry & H-J Lenz

  4. Unità di Oncologia, Istituto Scientifico San Raffaele, Milano, Italy

    V Ricci

  5. Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy

    F Graziano

  6. Department of Biomolecular Sciences, Section of Biochemistry and Molecular Biology, University of Urbino, Urbino, Italy

    A Ruzzo

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  1. F Loupakis
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  2. C Antoniotti
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  3. C Cremolini
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  4. W Zhang
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  5. D Yang
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  6. T Wakatsuki
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  7. P Bohanes
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  8. M Schirripa
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  9. L Salvatore
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  10. G Masi
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  11. V Ricci
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  12. F Graziano
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  13. A Ruzzo
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  14. L Benhaim
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  17. R El-Khoueiry
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  18. A Falcone
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Correspondence to F Loupakis.

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Loupakis, F., Antoniotti, C., Cremolini, C. et al. Prospective study of EGFR intron 1 (CA)n repeats variants as predictors of benefit from cetuximab and irinotecan in chemo-refractory metastatic colorectal cancer (mCRC) patients. Pharmacogenomics J 14, 322–327 (2014). https://doi.org/10.1038/tpj.2014.1

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  • DOI: https://doi.org/10.1038/tpj.2014.1

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