Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC) after adjuvant chemotherapy were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months or to undergo observation. The primary endpoint was DFS according to investigator assessment. This trial was terminated early. A total of 251 patients were randomized. Baseline characteristics were balanced among the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (hazard ratio (HR): 0.41, 95% confidence interval (CI), 0.27–0.62; P < 0.001) and overall survival (OS, HR: 0.56, 95% CI, 0.32–0.98; P = 0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27–0.61; P < 0.001) and OS (HR: 0.55, 95% CI, 0.32–0.96; P = 0.035) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P = 0.89) or OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to that reported previously for icotinib. Adjuvant icotinib for 12 months and 6 months following adjuvant chemotherapy provided a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months.