ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer

Abstract We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1 every 3 weeks) or IP (irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level. A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; P=0.082), median progression-free survival (PFS; 4.5 vs. 3.9 months, respectively; P=0.117) and overall survival (OS; 16.5 vs. 16.7 months, respectively; P=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, P=0.509; IP, 30.2% vs. 21.6%, respectively, P=0.536), median PFS (GP, 4.6 vs. 5.0 months, respectively, P=0.506; IP, 3.9 vs. 3.7 months, respectively, P=0.748) or median OS (GP, 18.6 vs. 11.9 months, respectively, P=0.070; IP, 17.5 vs. 14.0 months, respectively, P=0.821). Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC (NCT01003964).