Gefitinib is more effective in never-smokers with non-small-cell lung cancer: experience among Asian patients

Abstract

We retrospectively analysed the results of patients with advanced non-small-cell lung cancer treated with gefitinib to derive clinical factors predictive of response and a favourable survival outcome. Patients were treated with gefitinib 250 mg per day and reevaluated 4 -8 weeks later with repeat CT scan and every 8 weeks thereafter to assess response and the duration of response. Pathology review by a histopathologist was conducted, in particular to confirm a recently published result of bronchioloalveolar carcinoma histology or its components as predictive of response to gefitinib. Logistic regression and Cox regression analytical methods were applied to determine factors that could predict for response and improved overall survival. A total of 110 patients were treated. The overall response rate was 32% partial responses (PRs). Only never-smoking status was predictive of response in the logistic regression analysis, adjusted OR ¼ 6.1, 95% CI ¼ 1.7, 21.5. The presence of a PR and good performance status were predictive of a favourable survival outcome from the Cox regression modelling. Responders had an adjusted HR of 3.0, 95% CI ¼ 1.5 -5.8 compared to nonresponders, while patients with ECOG status 0 -1 had an adjusted HR of 0.42, 95% CI ¼ 0.25 -0.72, compared with patients with ECOG status 2 -4. Bronchioloalveolar carcinoma or its components were distinctly absent on pathology review. In conclusions, Never-smoking status is an important clinical predictor of a favourable response to gefitinib.

Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

“…Several subsequent retrospective studies have reported that female gender, adenocarcinoma histology, bronchioloalveolar subtype, never-smokers and patients with favourable PS are predictive factors of response Kim et al, 2005;Lim et al, 2005;Ando et al, 2006). EGFR mutation has been reported as a predictor of efficacy of gefitinib and erlotinib (Lynch et al, 2004;Pao et al, 2004).…”

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

“…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.…”

“…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.…”

“…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 favorable clinical outcome for NSCLC patients treated with gefitinib, especially those from East Asia.…”

“…(19,20) Some studies have suggested that smoking status can be a useful indicator when selecting candidate patients for gefitinib treatment. (3,21) Thus, it is important to discriminate the survival impact of EGFR mutation against those of clinicopathological factors in patients treated with gefitinib.…”