Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata.
Department of Cancer Information Research, National Hospital Organization Kyushu Cancer Center, Fukuoka; Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube.
Ann Oncol. 2019 Dec 1;30(12):1978-1984. doi: 10.1093/annonc/mdz399.
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 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.
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.
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.
三期研究 WJTOG 3405 的初步分析表明，与顺铂加多西他赛（CD）相比，表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）吉非替尼（G）在接受 EGFR 突变阳性非小细胞肺癌（NSCLC）一线治疗的 IIIB/IV 期或术后复发患者中具有更优的无进展生存期（PFS）。本报告呈现了最终的总生存期（OS）数据。
患者被随机分配至 G（250mg/天口服）和 CD（80mg/m2 静脉内）加多西他赛（60mg/m2 静脉内）组，每 21 天给药一次，最多给药 3-6 个周期。排除 5 例患者后，共有 172 例患者（每组 86 例，改良意向治疗人群）纳入生存分析。使用更新的数据（数据截止日期为 2013 年 9 月 30 日；中位随访时间 59.1 个月）重新评估 OS。采用 Kaplan-Meier 方法和对数秩检验进行分析，并使用 Cox 比例风险模型计算死亡的风险比（HRs）。
G 组和 CD 组的 OS 事件分别为 68（79.1%）例和 59（68.6%）例。G 组和 CD 组的中位生存时间分别为 34.9 个月和 37.3 个月，HR 为 1.252（95%CI：0.883-1.775，P=0.2070）。多变量分析确定术后复发和 IIIB/IV 期疾病为独立的预后因素，HR 为 0.459（95%CI：0.312-0.673，P<0.001）。G 组和 CD 组的中位生存时间（术后复发与 IIIB/IV 期疾病）分别为 44.5 个月和 27.5 个月，45.5 个月和 32.8 个月。
G 并未显示出优于 CD 作为一线治疗的 OS 获益。即使两组均有转移性疾病，术后复发患者的 OS 仍优于 IIIB/IV 期疾病患者。本研究在日本大学医院医学信息网络（UMIN）注册，注册号为 000000539。
