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.
Authors: Wang Si-Yu , Long Hao , Li Ning , Cheng Chao , Ou Wei , Yang Lin , You Jian , Liang Yi , Wang Bao-Xiao 
Published: June 2024

8004 Background: The efficacy, safety and ideal treatment duration of adjuvant icotinib (first-generation EGFR tyrosine kinase inhibitor) for patients with completely resected EGFR-mutated non-small-cell lung cancer (NSCLC) after adjuvant chemotherapy were not known in 2014, when this study was initiated. This phase 3 trial investigated whether icotinib following adjuvant chemotherapy improves clinical outcomes compared with observation in stage II-IIIA NSCLC harboring EGFR mutation. Methods: This is a multicenter, randomized, open-label, phase 3 trial. From July 2014 to December 2021, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were enrolled. Patients were assigned in a 1:1:1 ratio to receive icotinib (125mg, three times daily) for 12 months, icotinib for 6 months or to observation. The primary endpoint was disease-free survival (DFS) in the intention-to-treat population. Results: This trial was terminated early due to slow accrual.A total of 251 patients were randomized, with 84 patients in the 12-month icotinib group, 84 patients in the 6-month icotinib group, and 83 patients in the observation group. Baseline characteristics were balanced between the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (HR: 0.41, 95% CI, 0.27-0.62; P = 0.000025) 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 = 0.000014) and OS (HR: 0.55, 95% CI, 0.32-0.96; P = 0.035) compared with observation. Adjuvant icotinib of 12 months did not improve DFS (HR: 0.97; P = 0.89) and OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Median DFS was 61.8 months (95% CI, 43.3 to 80.3) for the 12-month icotinib group, 63.2 months (95% CI, 44.8 to 81.6) for the 6-month icotinib group compared with 23.7 months (95% CI, 16.5 to 30.9) for the observation group. The 5-year DFS and OS for the 12-month icotinib, 6-month icotinib and observation groups were 51.3%, 50.1% and 24.8%; and 74.5%, 74.0% and 65.1%; respectively. No differences in efficacy pertaining to icotinib duration were found in any of the subgroups. 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 the previous reports for icotinib. Conclusions: Adjuvant icotinib for 12 months and 6 months provide 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. Clinical trial information: NCT01996098 .