Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
Department of Oncology, Herlev University Hospital, Herlev, Denmark.
Lung Cancer. 2015 Nov;90(2):267-73. doi: 10.1016/j.lungcan.2015.08.003. Epub 2015 Aug 12.
OBJECTIVES: LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib+docetaxel versus placebo+docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib+docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. MATERIALS AND METHODS: The incidence and intensity of AEs were evaluated in all patients who received at least one dose of study medication (N=1307) and for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma (SCC; n=553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation, hypertension, bleeding, thromboembolic events, and skin disorders. RESULTS AND CONCLUSION: The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib+docetaxel versus 0.2% with placebo+docetaxel. The incidence of some events was higher with nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1-2 with both treatments. The incidence of all-grade bleeding was also slightly higher in nintedanib+docetaxel-treated patients (14.1% vs 11.6%) driven by between-treatment differences in the SCC subpopulation; most events were Grade 1-2. The proportion of patients with a thromboembolic event was low and comparable between arms for all grades (5.1% vs 4.6%) and Grade ≥3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with nintedanib+docetaxel. Survival benefits from addition of nintedanib to docetaxel in patients with adenocarcinoma after first-line therapy can be achieved alongside a manageable safety profile.
目的：LUME-Lung 1 是一项随机、安慰剂对照、III 期临床试验，旨在研究尼达尼布联合多西他赛与安慰剂联合多西他赛在一线化疗后进展的晚期 NSCLC 患者中的疗效。尼达尼布联合多西他赛可显著改善总人群的无进展生存期，并且在腺癌患者的预设分析中总生存期也显著改善。我们评估了与现有抗血管生成药物常见的特征性不良事件（AE）的发生频率。
材料和方法：在接受至少一剂研究药物的所有患者（N=1307）中评估 AE 的发生率和严重程度，并针对两种主要组织学类型进行评估：腺癌（n=653）和鳞状细胞癌（SCC；n=553）。通过类别、首选术语和最差 CTCAE 分级对特别关注的 AE 进行分析，包括穿孔、高血压、出血、血栓栓塞事件和皮肤疾病。
结果与结论：所有级别胃肠道（GI）穿孔患者的发生率较低，且在各治疗组之间（尼达尼布联合多西他赛组为 0.5%，安慰剂联合多西他赛组为 0.5%）和各组织学类型之间（尼达尼布联合多西他赛组为 0.5%，安慰剂联合多西他赛组为 0.5%）均保持平衡；非 GI 穿孔的发生率分别为尼达尼布联合多西他赛组 1.2%和安慰剂联合多西他赛组 0.2%。与安慰剂联合多西他赛相比，尼达尼布联合多西他赛组某些事件的发生率更高，包括高血压（3.5%比 0.9%）、皮疹（11.0%比 8.1%）和皮肤不良反应（13.0%比 10.7%）。皮疹和皮肤不良反应在两种治疗中主要为 1-2 级。尼达尼布联合多西他赛组全级别出血的发生率也略高（14.1%比 11.6%），这主要是由于 SCC 亚组中治疗间差异所致；大多数事件为 1-2 级。血栓栓塞事件的患者比例较低，各治疗组全级别（5.1%比 4.6%）和 3 级及以上（2.1%比 3.1%）事件的发生率均相当。LUME-Lung 1 研究的安全性评估表明，与其他抗血管生成药物相关的常见 AE 发生频率较低。尼达尼布联合多西他赛在一线治疗后进展的腺癌患者中的生存获益可与可管理的安全性特征同时实现。
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