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前瞻性、多中心、III期临床研究，纳入患者均为初治IIIb或IV期NSCLC患者，且携带19del或21L858R突变，PS评分为0-1分。符合入组标准的患者按照1:1的比例随机分为：
吉非替尼单药组(250 mg，口服，每日一次)
化疗(多西他赛60 mg/m2，第一天用药)联合顺铂(80mg/m2，第一天用药)
其中，化疗每21天为一个周期，应用3-6周期。进展后治疗方案由临床医生决定。研究的主要终点为PFS，次要研究终点为OS及ORR。
吉非替尼对比化疗可以明显延长EGFR突变NSCLC患者的中位PFS (吉非替尼9.2月vs化疗6.3月)。
两组的中位OS分别34.9个月和37.3个月，差异无统计学意义。
基于患者治疗顺序进行了进一步分析，以确定治疗顺序对患者OS的影响。吉非替尼组有55例患者出组后接受了双药含铂化疗(A组)，化疗组有78例患者出组后接受EGFR-TKI治疗(B组)，两组之间的中位OS分别为33.1个月和37.9个月，差异无统计学意义(HR=1.431, 95% CI: 0.966–2.119,P=0.0723)(图3)，但携带19del的患者首先接受化疗，进展后续贯吉非替尼治疗显示了有统计学意义的OS提高(31.8个月 vs. 41.6个月,HR=1.752, 95% CI: 1.001–3.065,P=0.047)，但在携带21L858R突变的患者中，并未观察到这一趋势(HR=1.118, 95% CI: 0.630–1.985,P=0.703)。
Background: Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data.
Patients and methods: Patients were randomized between G (250 mg/day orally) and cisplatin (80 mg/m2 intravenously) plus docetaxel (60 mg/m2 i.v.), administered every 21 days for three to six cycles. After the exclusion of 5 patients, 172 patients (86 in each group, modified intention-to-treat population) were included in the survival analysis. OS was re-evaluated using updated data (data cutoff, 30 September 2013; median follow-up time 59.1 months). The Kaplan-Meier method and the log-rank test were used for analysis, and hazard ratios (HRs) for death were calculated using the Cox proportional hazards model.
Results: OS events in the G group and CD group were 68 (79.1%) out of 86 and 59 (68.6%) out of 86, respectively. Median survival time for G and CD were 34.9 and 37.3 months, respectively, with an HR of 1.252 [95% confidence interval (CI): 0.883-1.775, P = 0.2070]. Multivariate analysis identified postoperative recurrence and stage IIIB/IV disease as independent prognostic factors, with an HR of 0.459 (95% CI: 0.312-0.673, P < 0.001). Median survival time (postoperative recurrence versus stage IIIB/IV disease) were 44.5 and 27.5 months in the G group and 45.5 and 32.8 months in the CD group, respectively.
Conclusion: G did not show OS benefits over CD as the first-line treatment. OS of patients with postoperative recurrence was better than that of stage IIIB/IV disease, even though both groups had metastatic disease.This study was registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.
Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. doi: 10.1093/annonc/mdz399. PMID: 31553438.
Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer - Annals of Oncology
Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. doi: 10.1016/S1470-2045(09)70364-X. Epub 2009 Dec 18. PMID: 20022809.
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