Safety and efficacy results of a phase IV, open-label, multicenter, safety-monitoring study of icotinib in treating advanced non-small cell lung cancer (NSCLC): ISAFE study.

Abstract

e19161 Background: The phase III ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS), based on which icotinib was approved by State Food and Drug Administration of China. We conducted a safety-monitoring study to assess the safety and efficacy of icotinib in a broad range of patients with advanced non-small-cell lung cancer (NSCLC) across China. Methods: This study was a single-arm, open-label, multi-center trial in advanced NSCLC patients who were suitable for treatment with oral icotinib 125 mg three times daily. Endpoints included safety, objective response rate (ORR) and disease control rate (DCR), were investigated overall and in subgroups. EGFR mutation analysis was performed retrospectively. Results: Between August, 2011 and August, 2012, 6,087 advanced NSCLC patients were registered with a median age of 63 years (range: 21-95 years), and 5,549 patients were evaluable for safety and tumor response. Baseline characteristics (%) were: male/female 50.8/49.2; non-smoker/ex- or current-smoker/no data 67.2/32.7/0.1; adenocarcinoma/non-adenocarcinoma/other 78.6/15.4/6.0; stage IIIB/IV/other 7.4/90.2/2.4; and 1,571(28.3%) patients were ≥ 70 years of age. The overall incidence of drug-related adverse events (AEs) of any grade was 31.5%, in which the most common drug-related AEs including rash (17.4%) and diarrhea (8.5%), and 3 patients experienced with interstitial lung disease (ILD) associated with icotinib. ORR and DCR were 30.0% and 80.6%, respectively. The safety in the elder patients (age ≥70, n=1,571) were similar to that in the overall population, the incidence of drug-related AEs of any grade was 30.6%, most of which were grade I or II. Among 989 patients who undertook EGFR mutation detection, 738 (74.6%) patients were mutation-positive with an ORR of 49.2% and a DCR of 92.3%. Moreover, in 251 (25.4%) wild type patients, the ORR and DCR were 17.8% and 75.7%, respectively. Conclusions: The data from over 6,000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated efficacy and a favorable toxicity profile in the routine clinical setting.