Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial

Abstract

Purpose: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results.

Methods: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data.

Results: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively.

Conclusion: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

FIG 1.

Consort diagram showing patient disposition for the ADJUVANT-CTONG1104 study (data cutoff: April 19, 2020). DFS, disease-free survival; EGFR, epidermal growth factor receptor; ITT, intention-to-treat; PP, per protocol; VP, vinorelbine plus cisplatin.

FIG 2.

Overall survival in the (A) ITT population and (B) PP population, and (C) subgroup analysis between gefitinib and VP groups. EGFR, epidermal growth factor receptor; HR, hazard ratio; ITT, intention-to-treat; PP, per protocol; VP, vinorelbine plus cisplatin. *Univariate test; †multivariate test.

FIG 3.

Subsequent treatment in the (A) ITT population, (B) overall survival, and (C) objective response rate for subsequent treatments. CR, complete response; DFS, disease-free survival; EGFR, epidermal growth factor receptor; NC, not calculable; NR, not reached; ITT, intention-to-treat; PD, progressive disease; PR, partial response; SD, stable disease; TKI, tyrosine kinase inhibitor; VP, vinorelbine plus cisplatin. *Univariate test.

FIG 4.

Updated disease-free survival for the (A) ITT and (B) PP populations. HR, hazard ratio; ITT, intention-to-treat; PP, per protocol; VP, vinorelbine plus cisplatin. *Univariate test.