title: 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.
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<and ⩾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.
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: F
authors: F
authors: Loupakis
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: C
authors: C
authors: Antoniotti
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: C
authors: C
authors: Cremolini
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: W
authors: W
authors: Zhang
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: D
authors: D
authors: Yang
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: T
authors: T
authors: Wakatsuki
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: P
authors: P
authors: Bohanes
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: M
authors: M
authors: Schirripa
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: L
authors: L
authors: Salvatore
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: G
authors: G
authors: Masi
authors: Unità di Oncologia, Istituto Scientifico San Raffaele, Milano, Italy.
authors: V
authors: V
authors: Ricci
authors: Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy.
authors: F
authors: F
authors: Graziano
authors: Section of Biochemistry and Molecular Biology, Department of Biomolecular Sciences, University of Urbino, Urbino, Italy.
authors: A
authors: A
authors: Ruzzo
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: L
authors: L
authors: Benhaim
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: F
authors: F
authors: Marmorino
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Y
authors: Y
authors: Ning
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: R
authors: R
authors: El-Khoueiry
authors: 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
authors: A
authors: A
authors: Falcone
authors: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: H-J
authors: HJ
authors: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007438:Introns; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin