Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study)
Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study)
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DOI：
10.1016/j.lungcan.2016.10.007
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发表时间：
2016-12-01
期刊：
影响因子：
5.3
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
--
作者：
Cicenas, Saulius;Geater, Sarayut Lucien;Wu, Yi-Long
目的：III 期 IUNO 试验评估了维持厄洛替尼与厄洛替尼相比，在四个周期的铂类化疗后未进展的晚期/转移性非小细胞肺癌 (NSCLC) 进展时的益处。 材料和方法：患者患有 IIIB/IV 期 NSCLC，没有已知的表皮生长因子受体 (EGFR) 激活突变，且在铂类诱导化疗后具有客观缓解或疾病稳定。局部检测后，对 EGFR 状态未知或野生型患者的肿瘤进行了中央 EGFR 突变检测。患者被随机分配接受盲法维持厄洛替尼 150 毫克/天（“早期厄洛替尼”）或安慰剂。服用安慰剂后病情出现进展的患者接受了开放标签厄洛替尼（“晚期厄洛替尼”）治疗；接受厄洛替尼治疗后病情进展的患者接受了批准的二线化疗或最佳支持治疗。主要终点：总生存期 (OS)。结果：643 名患者被随机分配接受厄洛替尼维持治疗 (n = 322) 或安慰剂 (n = 321)。截至 2015 年 3 月 23 日，“早期厄洛替尼”组发生了 242 例 (75.2%) OS 事件，而“晚期厄洛替尼”组发生了 235 例 (73.2%) 例 OS 事件。 “早期厄洛替尼”和“晚期厄洛替尼”的中位 OS 分别为 9.7 个月和 9.5 个月（HR，1.02，95% CI：0.85-1.22；对数秩 p = 0.82）。维持厄洛替尼未观察到无进展生存期、客观缓解率或疾病控制率获益。 410 名患者进入研究的二线阶段：160 名患者（50%）来自厄洛替尼维持组，250 名患者（78%）来自维持安慰剂组。不良事件（AE）的模式与之前的试验一致； 11 名接受盲法厄洛替尼治疗的患者和 3 名接受安慰剂治疗的患者在盲法维持阶段因非治疗相关 AE 死亡。结论：对于肿瘤不含有 EGFR 激活突变的患者，维持厄洛替尼治疗的 OS 并不优于二线治疗。安全性结果与厄洛替尼既定的安全性一致。因此，对于没有 EGFR 激活突变的晚期/转移性 NSCLC 患者，厄洛替尼维持治疗被认为是不利的。 (C) 2016 年作者。由爱思唯尔爱尔兰有限公司出版
Objective: The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed following four cycles of platinum-based chemotherapy.Materials and Methods: Patients had stage IIIB/IV NSCLC, no known epidermal growth factor receptor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-based induction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing. Patients were randomized to receive blinded maintenance erlotinib 150 mg/day ('early erlotinib') or placebo. Those who progressed on placebo received open-label erlotinib ('late erlotinib'); patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS).Results: 643 patients were randomized to receive maintenance erlotinib (n = 322) or placebo (n = 321). As of March 23, 2015, 242 (75.2%) OS events had occurred with 'early erlotinib' versus 235 (73.2%) with 'late erlotinib'. Median OS was 9.7 and 9.5 months with 'early erlotinib' and 'late erlotinib', respectively (HR, 1.02, 95% CI: 0.85-1.22; log-rank p = 0.82). No progression-free survival, objective response rate, or disease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%) from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previous trials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs.Conclusions: OS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with the established safety profile of erlotinib. Thus, maintenance treatment with erlotinib in patients with advanced/metastatic NSCLC without EGFR-activating mutations is considered unfavorable. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.