Adjuvant icotinib for resected EGFR-mutated stage II-IIIA non-small-cell lung cancer (ICTAN, GASTO1002): a randomized comparison study

Abstract

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC) were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial (GASTO1002, NCT01996098), patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after 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 disease-free survival (DFS). This trial was terminated early. A total of 251 patients were randomized. Adjuvant icotinib for 12 months significantly improved DFS (hazard ratio [HR]: 0.40, 95% confidence interval [CI], 0.27-0.61; P < 0.001) and overall survival (OS; HR: 0.55, 95% CI, 0.32-0.96; P = 0.032) compared with observation. Adjuvant icotinib of 6 months also significantly improved DFS (HR: 0.41, 95% CI, 0.27-0.62; P < 0.001) and OS (HR: 0.56, 95% CI, 0.32-0.98; P = 0.038) 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%, 6.0% and 2.4% for the 12-month icotinib, 6-month icotinib, and observation groups, respectively. Adjuvant icotinib for 12 months or 6 months following adjuvant chemotherapy improved DFS and OS compared with observation in patients with resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile, supporting it as a potential treatment option.

Fig. 1

Trial profile. All randomized patients were included in the ITT population for efficacy analyses. Safety analyses were performed for all patients who received icotinib and those in the observation group. ITT, intention-to-treat; N number

Fig. 2

Kaplan-Meier estimates of DFS by the investigator in the ITT population. DFS disease-free survival, HR hazard ratio, CI confidence interval, ITT intention-to-treat

Fig. 3

Forest plots of DFS by subgroup, according to investigator assessment. a Subgroup analyses of DFS for 12-month icotinib versus observation. b Subgroup analyses of DFS for 6-month icotinib versus observation. Subgroups were either pre-planned (sex, stage, and EGFR mutation type) or post hoc (age, smoking history, N stage, and side). DFS disease-free survival, HR hazard ratio, CI confidence interval, EGFR epidermal growth factor receptor

Fig. 4

Kaplan-Meier estimates of OS in the ITT population. OS, overall survival; HR, hazard ratio; CI, confidence interval; ITT, intention-to-treat