Gefitinib (G) versus vinorelbine+cisplatin (VP) as adjuvant treatment in stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC) with EGFR-activating mutation (ADJUVANT): A randomized, Phase III trial (CTONG 1104).

8500 Background: Cisplatin-based adjuvant chemotherapy is standard of care for patients (pts) with stage II-IIIA non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have shown no benefits in the adjuvant setting for pts with unselected resected NSCLC in the BR19 and RADIANT trials. ADJUVANT (NCT01405079) is the first randomized trial to compare gefitinib (G) with vinorelbine+cisplatin (VP) in completely resected pathological stage II-IIIA (N1-N2) NSCLC with EGFR-activating mutation. Methods: Completely resected stage II-IIIA (N1-N2) NSCLC pts with EGFR-activating mutation were randomized 1:1 to receive G (250 mg once daily) for 24 months or vinorelbine (25 mg/m 2 Day 1 and Day 8) plus cisplatin (75 mg/m 2 Day 1) every 3 weeks for 4 cycles. Stratification factors were lymph node status (pN1/N2) and EGFRmutation status. The primary endpoint was disease-free survival (DFS) in the intent-to-treat population. Results: A total of 222 pts were randomly assigned (Sep 19 2011 to Apr 24 2014). Baseline characteristics were balanced. At the time of data cutoff, the median duration of treatment was 21.9 months in the G arm, and 4 cycles in the VP arm. The median follow-up period was 36.5 months (range 0.1 to 62.8). G had significantly longer median DFS (28.7 months, 95% confidence interval [CI] 24.9 to 32.5) than VP (18.0 months, 95% CI 13.6 to 22.3; hazard ratio 0.60; 95% CI 0.42 to 0.87; p= 0.005). 3-year DFS was significantly better with G (34.0% vs 27.0%; p= 0.013). The number of overall survival events was 76 (34.2%). In the subgroup analysis of patients treated with G, lymph node status (pN1/N2) demonstrated significant correlation with DFS ( p< 0.05). Grade 3 or higher adverse events were less common with G than with VP (12.3% vs 48.3%; p< 0.001). No interstitial lung disease was observed with G. Conclusions: Adjuvant G significantly prolonged DFS compared with VP in pts with resected stage II-IIIA (N1-N2) NSCLC with EGFR-activating mutation. Adjuvant gefitinib should be considered as an important option for stage II-IIIA lung cancer pts with EGFR mutation. Clinical trial information: NCT01405079.