Identifying patients with non-small cell lung cancer (NSCLC) unlikely to benefit from erlotinib: An exploratory analysis of National Cancer of Institute of Canada Clinical Trials Group BR.21

Abstract

7161 Background: Despite a 9% response rate, BR.21 demonstrated significant survival benefit for patients receiving erlotinib as 2nd/3rd line therapy for NSCLC. We undertook to characterize, by exploratory subset analysis, patients less likely to benefit from erlotinib. To identify factors for consideration, we first identified baseline characteristics associated with early progression by eight wks and early death by 3 mos. Methods: Using stratification factors and potential prognostic factors from BR.21, the Cox regression model with stepwise selection was used to establish a prognostic model to separate erlotinib patients into 4 risk categories based on the 10th, 50th & 90th percentiles of prognostic index scores. 7 variables (smoking history, PS, weight loss, anemia, high LDH, response to prior chemo and time from diagnosis to randomization) were used in the final model. The hypothesis was that the characteristics of the treated patients in the highest risk group would also be predictive of lack of benefit from erlotinib when erlotinib and placebo patients with the same characteristics were compared. Results: Factors associated with PD by 8 wks were: PS2–3 (p = 0.009), weight loss (p = 0.0004), anemia (p = 0.008), PD to prior chemo (p = 0.006), non-Asian (p = 0.047), EGFR IHC-negative (p = 0.005), Factors associated with survival < 3 mos were: PS2–3 (p < 0.0001), weight loss (p < 0.0001), anemia (p < 0.0001), PD to prior chemo (p < 0.0001), non-Asian (p = 0.008), high LDH (p < 0.0001), time to randomization <12 mos (p = 0.0003). Comparison of overall survival for the 4 risk groups derived from prognostic index score as follows: high benefit (HR = 0.41, p = 0.007), 2 intermediate benefit (HR 0.79, p = 0.09; HR 0.80; p = 0.09); no benefit (HR 1.23; p = 0.42). Median survivals for erlotinib (placebo) patients in each group were 17.3 (8.3), 9.7 (7.5), 4.1 (3.7), 1.9 (2.7) mos. Conclusions: By establishing a prognostic model, we identified a small group of patients who are unlikely to benefit from 2nd/3rd line erlotinib therapy. This model requires prospective validation to confirm that it is both prognostic and predictive of outcome from treatment. [Table: see text]