- 作者：Giulio Metro ; Rita Chiari ; Simona Duranti ; Annamaria Siggillino ; Matthias J. Fischer ; Diana Giannarelli ; Vienna Ludovini ; Chiara Bennati ; Luca Marcomigni ; Alice Baldi ; Michele Giansanti ; Vincenzo Minotti ; Lucio Crin¨°
- 关键词：EGFR ; Erlotinib ; EGFR-TKI ; Gefitinib ; KRAS ; Non-small cell lung cancer
- 刊名：Lung Cancer
- 出版年：2012
- 出版时间：October, 2012
- 年：2012
- 卷：78
- 期：1
- 页码：81-86
- 全文大小：567 K
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.