Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib‐treated patients with lung adenocarcinoma

Abstract

Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinibtreated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy. EGFR mutations in exon19 and exon21 named drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Drugsensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex, and smoking status showed that drug-sensitive EGFR mutations were significantly related to longer overall survival (OS) (P < 0.001) and progressionfree survival (PFS) (P < 0.001). In addition, we investigated the impact of sex and smoking status according to EGFR mutation status, and the impact of EGFR mutation status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with longer OS and PFS according to EGFR mutation status. Drug-sensitive EGFR mutations were significantly associated with longer OS and PFS according to sex or smoking status. Our results indicated that drug-sensitive EGFR mutations were the only independent factor for longer survival of patients treated with gefitinib, suggesting that patient selection based on EGFR mutation status for gefitinib therapy will lead to a better outcome for patients with lung adenocarcinoma. (Cancer Sci 2008; 99: 303-308) E pidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is highly expressed in cancer cells.(1) Gefitinib and erlotinib are reversible EGFR tyrosine kinase inhibitors (EGFR-TKI) used for the treatment of non-small-cell lung cancer (NSCLC) patients.(2) Previous studies have focused on identifying factors that are useful indicators when selecting candidate patients for gefitinib treatment. An adenocarcinoma histology, female sex, a never-smoking status, and an East Asian ethnicity are clinicopathological factors that are associated with sensitivity to gefitinib and these factors can be indicators for gefitinib therapy. (2,3) Mutations in EGFR have been reported, particularly in NSCLC.(1,4,5) EGFR mutations are frequently located in exon19 and exon21 of the EGFR tyrosine kinase domain and play an oncogenic role in adenocarcinoma.(6) Previous studies have shown that a positive EGFR mutation status is significantly related to adenocarcinoma histology, female sex, a never-smoking status, and an East Asian ethnicity.(4,5,7-10) Of clinical interest, approximately 80% of patients with the EGFR mutation, especially exon19 deletions and the L858R mutation at exon21, are associated with sensitivity to reversible EGFR-TKIs. Positive EGFR mutation status is considered to predict a ...

Gefitinib for a Poor Performance Status Patient with Squamous Cell Carcinoma of the Lung Harboring <i>EGFR</i> Mutation

“…Several recent papers have suggested that tumor molecular profiling may supersede these clinical selection factors for EGFR-TKI treatment in patients with NSCLC. Toyooka et al reported that EGFR mutation was independently associated with a favorable prognosis in gefitinibtreated patients regardless of gender or smoking history (6). In the present case, EGFR mutation was detected in a male, currently smoking, SCC patient, indicating that EGFR mutational analysis is more important than clinical characteristics and histology.…”

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

“…In EGFR-mutant cases, EGFR-TKIs would be expected to be effective and long-term survival could be expected with local treatment of cases of localized recurrence, such as cases 3 and 6 in Table VI. Our study demonstrated that bilateral/contralateral lung recurrence was significantly more frequent among EGFR+ cases. In those cases, long-term survival may be achieved with combination therapy, consisting of EGFR-TKI treatment, cytotoxic chemotherapy and local treatment, for each lesion (21)(22)(23)(24). In general, long post-recurrence survival may be expected in patients with slow-growing tumors or long recurrence-free survival; however, no association between post-recurrence survival time and recurrence-free survival time according to EGFR mutations was observed in this study.…”

Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers

“…EGFR mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung ADC. Patient's sex and smoking status were not significantly associated with longer overall survival and progression-free survival according to EGFR mutation status [26]. Patients with advanced NSCLC who were selected on the basis of EGFR mutations improved progression-free survival with acceptable toxicity but those with no EGFR mutation did not.…”