S.G. Moscati Hospital, Avellino, Italy.
J Clin Oncol. 2012 Aug 20;30(24):3002-11. doi: 10.1200/JCO.2011.41.2056. Epub 2012 Jul 9.
Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence.
Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned.
At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation.
In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
厄洛替尼可延长不适合进一步化疗的晚期非小细胞肺癌（NSCLC）患者的生存时间，并且两项 II 期研究表明其可能是一线化疗的替代方案。一项随机 III 期试验旨在检验一线厄洛替尼治疗进展后序贯顺铂-吉西他滨是否在生存方面不劣于标准反序。
纳入 IIIB 期（有胸腔积液或锁骨上淋巴结转移）至 IV 期 NSCLC 患者，表现状态为 0 至 1 分。通过 95%CI 上限为 1.25 的死亡风险比（HR），80%的效能，单侧α值为.025，以及两次中期分析，计划入组 900 例患者。
在第一次预定的中期分析中，当事件数达到一半时，下限已经超过，独立数据监测委员会建议提前终止该研究。760 例患者（中位年龄为 62 岁，范围为 27 至 81 岁）被随机分配。两组患者的基线特征均衡。截至 2011 年 6 月 1 日，中位随访时间为 24.3 个月，记录了 536 例死亡（标准治疗组 263 例，实验组 273 例）。标准治疗组的中位生存时间为 11.6 个月（95%CI，10.2 至 13.3 个月），实验组为 8.7 个月（95%CI，7.4 至 10.5 个月）。实验组的死亡调整 HR 为 1.24（95%CI，1.04 至 1.47）。性别、吸烟习惯、组织学类型和表皮生长因子受体（EGFR）突变对结果无影响。
在未经选择的晚期 NSCLC 患者中，与标准一线化疗序贯厄洛替尼相比，一线厄洛替尼治疗进展后序贯顺铂-吉西他滨的总体生存时间明显更差。
