Long-term outcomes of neoadjuvant gefitinib in resectable stage II-IIIA non-small cell lung cancer: A phase II, prospective cohort study

被引：0
作者：
Ma, Zhanming [1 ,2 ,3 ,4 ]
Fu, Fangqiu [1 ,2 ,3 ,4 ]
Zhang, Yang [1 ,2 ,3 ,4 ]
Chen, Haiquan [1 ,2 ,3 ,4 ]
机构：
[1] Fudan Univ, Shanghai Canc Ctr, Dept Thorac Surg, 270 DongAn Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Canc Ctr, State Key Lab Genet Engn, 270 DongAn Rd, Shanghai 200032, Peoples R China
[3] Fudan Univ, Inst Thorac Oncol, Shanghai 200032, Peoples R China
[4] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
来源：
LUNG CANCER | 2025年 / 201卷
基金：
中国国家自然科学基金;
关键词：
Non-small cell lung carcinoma; Epidermal growth factor receptor; Neoadjuvant therapy; Gefitinib; Major pathological response; Recurrence pattern; 1ST-LINE TREATMENT; EGFR MUTATIONS; OPEN-LABEL; CHEMOTHERAPY; ERLOTINIB; SURVIVAL; EPIDEMIOLOGY; MULTICENTER; PROGRESSION;
D O I：
10.1016/j.lungcan.2025.108457
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Our previous study has showed the safety and efficacy of preoperative gefitinib in patients with stage II-IIIA resectable non-small cell lung cancer (NSCLC). This study aimed to report the long-term survival analysis and recurrent patterns. Methods: This was a single-arm, phase II clinical trial. Patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations were enrolled. Patients were administrated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints included the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival (OS). MPR was defined as the presence of no more than 10 % viable tumor. Chi-square test was used to assess the differences in CNS recurrence rates and recurrent patterns. Results: Of the 33 intention-to-treat patients, ORR was 54.5 % (95 % confidence interval (CI), 37.7-70.7), and the rate of MPR was 24.2 % (95 % CI, 11.9-40.4). Among the investigated 28 patients, the median follow-up was 108.5 months. The median OS was 89.8 months (95 % CI, 44.37-NC), and the median DFS was 36.4 months (95 % CI, 18.9-NC). In addition, MPR continued to indicate significantly improved DFS, as well as OS (DFS, p = 0.015; OS, p = 0.037). The neoadjuvant gefitinib group showed prolonged DFS and OS than platinum doublet group (hazard ratio (HR) = 1.71, 95 % CI, 1.02-2.85, p = 0.038; and HR = 2.31; 95 % CI, 1.28-4.16, p = 0.0044, respectively). There was a significant difference in the distant recurrence patterns between the two groups (p = 0.032). Moreover, the gefitinib group showed similar overall brain metastasis rate than platinum doublet group (21.4 % versus 27.5 %). Conclusions: With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA EGFR-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.
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页数：8
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共 29 条
[1]  
Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin., 68, 6, pp. 394-424, (2018)
[2]  
Cao M., Chen W., Epidemiology of lung cancer in China, Thorac Cancer., 10, 1, pp. 3-7, (2019)
[3]  
Asamura H., Chansky K., Crowley J., Et al.
[4]  
Casal-Mourino A., Ruano-Ravina A., Lorenzo-Gonzalez M., Et al., Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival, Transl Lung Cancer Res., 10, 1, pp. 506-518, (2021)
[5]  
Lv C., Fang W., Wu N., Et al., Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial, Lung Cancer, 178, pp. 151-156, (2023)
[6]  
Zhang Y., Fu F., Hu H., Et al.
[7]  
Shi Y., Au J.S., Thongprasert S., Et al., A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER), J Thorac Oncol., 9, 2, pp. 154-162, (2014)
[8]  
Lu S., Kato T., Dong X., Et al., Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC, N Engl J Med., 391, 7, pp. 585-597, (2024)
[9]  
Ramalingam S.S., Vansteenkiste J., Planchard D., Et al., Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC, N Engl J Med., 382, 1, pp. 41-50, (2020)
[10]  
Soria J.C., Ohe Y., Vansteenkiste J., Et al., Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer, N Engl J Med., 378, 2, pp. 113-125, (2018)
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