Cicènas Saulius, Geater Sarayut Lucien, Petrov Petar, Hotko Yevgeniy, Hooper Gregory, Xia Fan, Mudie Nadejda, Wu Yi-Long
VU, MF, National Cancer Institute, Santariskiu 1, LT-08660 Vilnius, Lithuania.
Division of Respiratory and Respiratory Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Rd., Hat Yai, Songkhla 90110, Thailand.
Lung Cancer. 2016 Dec;102:30-37. doi: 10.1016/j.lungcan.2016.10.007. Epub 2016 Oct 20.
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.
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 150mg/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).
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.
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.
III期IUNO试验评估了在接受四个周期铂类化疗后未进展的晚期/转移性非小细胞肺癌（NSCLC）中，维持使用厄洛替尼与疾病进展时使用厄洛替尼相比的获益情况。
患者患有IIIB/IV期NSCLC，无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有客观缓解或疾病稳定。对局部检测后EGFR状态未知或为野生型的患者的肿瘤进行中心EGFR突变检测。患者被随机分组，接受盲法维持使用厄洛替尼150mg/天（“早期厄洛替尼”）或安慰剂。在安慰剂组中病情进展的患者接受开放标签的厄洛替尼（“晚期厄洛替尼”）；在厄洛替尼组中病情进展的患者接受批准的二线化疗或最佳支持治疗。主要终点：总生存期（OS）。
643例患者被随机分组接受维持使用厄洛替尼（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，“晚期厄洛替尼”组发生了235例（73.2%）。“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（风险比[HR]，1.02，95%置信区间[CI]：0.85 - 1.22；对数秩检验p = 0.82）。维持使用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方面的获益。410例患者进入研究的二线阶段：160例（50%）来自维持使用厄洛替尼组，250例（78%）来自维持使用安慰剂组。不良事件（AE）模式与既往试验一致；11例接受盲法厄洛替尼治疗的患者和3例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。
对于肿瘤未携带EGFR激活突变的患者，维持使用厄洛替尼的总生存期并不优于二线治疗。安全性结果与厄洛替尼已确立的安全性特征一致。因此，在无EGFR激活突变的晚期/转移性NSCLC患者中使用厄洛替尼进行维持治疗被认为是不利的。
