INTRODUCTION: This retrospective study was undertaken to investigate the impact of specific mutant KRAS on clinical outcome to either gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) in patients with EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC). METHODS: Patients with an EGFR WT genotype who were treated with an EGFR-TKI for advanced disease at our Institution were identified. Simultaneous availability of KRAS mutation status was required for study inclusion. RESULTS: Sixty-seven patients were eligible. Median age was 60 years (39-84), and 10 patients (14.9%) had received an EGFR-TKI as upfront therapy. Overall, the median progression-free survival (PFS) and overall survival (OS) were 2.9 months and 18.0 months, respectively. KRAS mutant patients (n=18) experienced a significantly shorter PFS compared with those carrying a KRAS WT genotype (n=49) (1.6 months vs 3.0 months, respectively, P=0.04; HR=1.92). However, within the KRAS mutant group a great variability in terms of sensitivity to treatment was noted (PFS ranging from 0.7 months to 38.7 months). KRAS codon 13 mutant patients (n=4) experienced the worse outcome when compared with KRAS codon 12 mutants (n=14) and KRAS WT patients (P<0.0001 and P=0.01 for PFS and OS, respectively). CONCLUSIONS: Though we found that EGFR WT/KRAS mutant advanced NSCLC patients are associated with an increased resistance to treatment, specific mutant KRAS may account for differential sensitivity to an EGFR-TKI. KRAS codon 13 mutants are those who seem to experience the worse clinical outcome.
INTRODUCTION: This retrospective study was undertaken to investigate the impact of specific mutant KRAS on clinical outcome to either gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) in patients with EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC). METHODS:Patients with an EGFR WT genotype who were treated with an EGFR-TKI for advanced disease at our Institution were identified. Simultaneous availability of KRAS mutation status was required for study inclusion. RESULTS: Sixty-seven patients were eligible. Median age was 60 years (39-84), and 10 patients (14.9%) had received an EGFR-TKI as upfront therapy. Overall, the median progression-free survival (PFS) and overall survival (OS) were 2.9 months and 18.0 months, respectively. KRAS mutant patients (n=18) experienced a significantly shorter PFS compared with those carrying a KRAS WT genotype (n=49) (1.6 months vs 3.0 months, respectively, P=0.04; HR=1.92). However, within the KRAS mutant group a great variability in terms of sensitivity to treatment was noted (PFS ranging from 0.7 months to 38.7 months). KRAS codon 13 mutant patients (n=4) experienced the worse outcome when compared with KRAS codon 12 mutants (n=14) and KRAS WTpatients (P<0.0001 and P=0.01 for PFS and OS, respectively). CONCLUSIONS: Though we found that EGFR WT/KRAS mutant advanced NSCLCpatients are associated with an increased resistance to treatment, specific mutant KRAS may account for differential sensitivity to an EGFR-TKI. KRAS codon 13 mutants are those who seem to experience the worse clinical outcome.
Authors: George Mulligan; David I Lichter; Alessandra Di Bacco; Stephen J Blakemore; Allison Berger; Erik Koenig; Hugues Bernard; William Trepicchio; Bin Li; Rachel Neuwirth; Nibedita Chattopadhyay; Joseph B Bolen; Andrew J Dorner; Helgi van de Velde; Deborah Ricci; Sundar Jagannath; James R Berenson; Paul G Richardson; Edward A Stadtmauer; Robert Z Orlowski; Sagar Lonial; Kenneth C Anderson; Pieter Sonneveld; Jesús F San Miguel; Dixie-Lee Esseltine; Matthew Schu Journal: Blood Date: 2013-12-11 Impact factor: 22.113
Authors: B Ricciuti; M Brambilla; A Cortellini; A De Giglio; C Ficorella; A Sidoni; G Bellezza; L Crinò; V Ludovini; S Baglivo; G Metro; R Chiari Journal: Clin Transl Oncol Date: 2019-07-22 Impact factor: 3.405
Authors: Emma Shtivelman; Thomas Hensing; George R Simon; Phillip A Dennis; Gregory A Otterson; Raphael Bueno; Ravi Salgia Journal: Oncotarget Date: 2014-03-30