9 vs 6.1 months; hazard ratio [HR]: 0.67, p = .012) and in patients check details of Asian origin (median survival, 9.5 vs 5.5 months; HR: 0.66, p = .01). A later exploratory biomarker analysis found a numeric (but not statistically significant) RR benefit with gefitinib in patients with EGFR protein-expressing tumors as well as those with high EGFR copy numbers. Patients whose tumors expressed EGFR protein also had a numerically greater survival benefit (HR: 0.77; p = .126) compared
with those whose tumors did not express EGFR (HR: 1.57; p = 0.14). The presence of somatic mutations in EGFR Exons 19 and 21 also appeared to predict response (RR, 37.5% vs 2.6%; p-value not reported) . Another phase 3 trial evaluating gefitinib in lung cancer called INTEREST (Iressa Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere), conducted in 1466 patients with NSCLC who had received 1 or 2 prior chemotherapy
regimens, found gefitinib to be non inferior for survival (median OS of 7.6 months; 1-year survival of 32%) compared with docetaxel, and offered improved tolerability and patient quality of life. Preplanned subgroup analyses found one significant difference between the treatment groups: patients who had received 2 prior chemotherapy regimens had better survival with docetaxel than with gefitinib (p = .031). Overall, among patients taking gefitinib, 2.2% had grade 3/4 hematologic PD-0332991 in vivo AEs, whereas docetaxel-treated patients had a 58.2% incidence of grade 3/4 neutropenia and a 42.3% incidence of grade 3/4 leukopenia . Erlotinib has shown a significant improvement in median survival, quality of life, and related symptoms in an unselected population of advanced and metastatic NSCLC patients in the second or third-line setting and most recently in maintenance therapy. National Cancer Institute of Canada Clinical Trials Group conducted a phase III randomized trial, named BR.21,
in which erlotinib was compared with placebo in stage III/IV NSCLC patients who had failed first- or second-line chemotherapy. A total of 731 patients Non-specific serine/threonine protein kinase were randomized in a 2:1 ratio to receive either erlotinib at 150 mg/day or placebo. Those patients had metastatic NSCLC that had previously been treated with one standard chemotherapy regimen (50% of patients) or with two chemotherapy regimens (50% of patients). Almost all patients received platinum-based chemotherapy. The OR rate was 8.9% in the erlotinib arm and 1% in the placebo group. The median durations of response were 7.9 months and 3.7 months, respectively. The median over-all survival time was 6.7 months for those in the erlotinib regimen compared with 4.7 months for those in the placebo arm. ORs were more frequent in women (14% vs 6%), in patients with adenocarcinoma, as compared with other histotypes (14% vs 4.1%), and in patients without a smoking history (25% vs 4%) .