EGFR-TKI靶向治疗非小细胞肺癌研究进展.ppt

ISEL (IRESSA Survival Evaluation in Lung cancer), a randomised, double-blind, placebo-controlled, parallel-group, multicentre, Phase III trial, was designed to investigate the effect on survival of gefitinib 250 mg/day plus best supportive care (BSC) in patients with NSCLC who were refractory to, or intolerant of, their most recent chemotherapy regimen.1 The primary endpoint of ISEL was survival in the overall and adenocarcinoma patient populations. Secondary endpoints included time to treatment failure (TTF), ORR, QoL and symptom improvement and safety. Eligible patients were 18 years old, had received 1 or 2 prior therapies for NSCLC, and were refractory to or intolerant of their most recent chemotherapy regimen. Patients were stratified initially according to tumour histology, sex, smoking history, number of prior chemotherapy regimens, reason for failure of prior chemotherapy and performance status (PS). Prior to unblinding, the following additional patient subgroups were added to the statistically rigorous subgroup analysis: prior docetaxel treatment; age at randomisation; time from diagnosis to treatment; racial origin; and best response to prior chemotherapy. Patients were randomised in a 2:1 ratio to receive gefitinib or placebo, and received BSC according to local practice. At a median follow-up of 7.2 months (range 3-15 months), 976 deaths had occurred in the ISEL trial and the total mortality rate was 58%. In the overall population the improvement in survival with IRESSA did not reach statistical significance compared with placebo (Log-rank hazard ratio [HR] 0.89; 95% [CI] 0.77, 1.02; p=0.087).1 However, a supportive Cox proportional hazards analysis suggested statistical significance in favour of IRESSA (HR 0.86; 95% CI 0.76, 0.99; p=0.030). Median survival in the overall population was 5.6 months for IRESSA compared with 5.1 months for placebo.1 Estimated 1-year survival rates for IRESSA and placebo were 27% and 21%, respectively, in the overall po