Study | Agent | Subject and level of evidence | Patients n | RR % | PFS months | HR (95% CI) | OS months | HR (95%CI) | Interaction p-value |
Douillard [16] (INTEREST Study) | Gefitinib | RCT and PRES second-line: gefitinib versus docetaxel | Positive: 258 | 9 versus 11; p = 0.66 | 1.6 versus 2.8 | 1.29 (0.98–1.70); p = 0.7 | 7.9 versus 6.5 | 1.0 (0.77–1.29); p = 0.98 | OS: p = 0.87 |
Negative: 87 | 15.8 versus 6.1; p = 0.27 | 2.9 versus 3.0 | 0.90 (0.53–1.52); p = 0.69 | 7.5 versus 9.2 | 1.0 (0.65–1.55); p = 0.99 | ||||
Hirsch [17] (ISEL Study) | Gefitinib | RCT and URES second- or third-line: gefitinib versus placebo | Positive: 264 | 8.2 versus 1.5; p = NA | 2.8 versus 3.2 | 0.83# (0.61–1.12); p = ns | 5.5 versus 4.6 | NA | OS: p = 0.049 |
Negative: 115 | 1.5 versus 0; p = NA | 1.9 versus 3.9 | 1.24# (0.77–2.02); p = ns | 4.2 versus NR | NA | ||||
Tsao [18] (BR21 Study) | Erlotinib | RCT and PRES second- or third-line: erlotinib versus placebo | Positive: 106 | 12 versus 3; p = 0.10¶ | NA | NA | NA | 0.68+ (0.49–0.95); p = 0.02 | OS: p = 0.25 |
Negative: 80 | 0.93+ (0.63–1.36); p = 0.70 |
RR: response rate; PFS: progression-free survival; HR: hazard ratio; OS: median overall survival; INTEREST: Iressa NSCLC Trial Evaluating Response and Survival Versus Taxotere; RCT: randomised clinical phase III trial; PRES: pre-planned retrospective exploratory study; ISEL: Iressa Survival Evaluation in Lung Cancer; URES: unplanned retrospective exploratory study; NA: not available; ns: nonsignificant difference; NR: not reached. #: time to treatment failure; ¶: erlotinib group only; +: erlotinib versus placebo group.