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.

• Authors: Wen-Zhao Zhong, Qun Wang, Wei-Min Mao, Song-Tao Xu, Lin Wu, Yu-Cheng Wei, Yong-Yu Liu, Chun Chen, Ying Cheng, Rong Yin, Fan Yang, Sheng-Xiang Ren, Xiao-Fei Li, Jian Li, Cheng Huang, Zhi-Dong Liu, Shun Xu, Ke-Neng Chen, Shi-Dong Xu, Lun-Xu Liu, Ping Yu, Bu-Hai Wang, Hai-Tao Ma, Jin-Ji Yang, Hong-Hong Yan, Xue-Ning Yang, Si-Yang Liu, Qing Zhou, Yi-Long Wu
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 39 Issue 7 Pg. 713-722 (03 01 2021) ISSN: 1527-7755 [Electronic] United States
• PMID: 33332190 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• EGFR protein, human
• ErbB Receptors
• Cisplatin
• Vinorelbine
• Gefitinib

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality, pathology)
• Chemotherapy, Adjuvant
• China
• Cisplatin (adverse effects, therapeutic use)
• Disease-Free Survival
• ErbB Receptors (genetics)
• Female
• Gefitinib (adverse effects, therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Time Factors
• Vinorelbine (adverse effects, therapeutic use)