title: The prevalent KRAS exon 2 c.35 G>A mutation in metastatic colorectal cancer patients: A biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?
abstract: Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G>A KRAS mutation was retrospectively evaluated. Fit c.35 G>A mutant patients showed significantly worse OS compared to wild-type and to other mutant. After progression and in unfit patients, c.35 G>A mutation affected significantly worse PFS and OS. c.35 G>A mutant status does not significantly affect worse PFS in patients fit for first line FIr-B/FOx, and it may depend upon effectiveness of anti-VEGF-containing intensive regimen.
authors.affiliation: Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Bruera
authors.affiliation: Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Cannita
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessitore
authors.affiliation: Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.affiliation: Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Ficorella
authors.affiliation: Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. Electronic address: enrico.ricevuto@univaq.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ricevuto
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005091:Exons; D005838:Genotype; D006801:Humans; D009154:Mutation; D059645:Mutation Rate; D009362:Neoplasm Metastasis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Bevacizumab; Biomarker; Intensive regimens; KRAS c.35 G>A mutation; Metastatic colorectal cancer