Heymach John V, Johnson Bruce E, Prager Diane, Csada Edit, Roubec Jaromír, Pesek Milos, Spásová Irena, Belani Chandra P, Bodrogi István, Gadgeel Shirish, Kennedy Sarah J, Hou Jeannie, Herbst Roy S
Dana-Farber Cancer Institute, Boston, MA, USA.
J Clin Oncol. 2007 Sep 20;25(27):4270-7. doi: 10.1200/JCO.2006.10.5122.
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC).
This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability.
In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval.
The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.
凡德他尼是一种每日一次的口服制剂，可抑制血管内皮生长因子受体-2以及表皮生长因子受体激酶活性。本研究评估了凡德他尼联合多西他赛在既往接受过治疗的非小细胞肺癌（NSCLC）患者中的活性。
这项两部分的研究包括一个开放标签导入期和一个双盲随机期。符合条件的患者在一线铂类化疗失败后患有局部晚期或转移性（IIIB/IV期）NSCLC。随机期的主要目标是延长接受凡德他尼（100或300mg/天）联合多西他赛（75mg/m²静脉输注，每21天一次）的患者相较于接受安慰剂联合多西他赛的患者的无进展生存期（PFS）。该研究旨在拥有超过75%的检验效能，以在单侧显著性水平P <.20时检测出50%的延长。次要目标包括客观缓解率、总生存期、安全性和耐受性。
在随机期（n = 127），凡德他尼100mg联合多西他赛组（n = 42；与多西他赛相比的风险比 = 0.64；单侧P = 0.037）的中位PFS为18.7周；凡德他尼300mg联合多西他赛组（n = 44；与多西他赛相比的风险比 = 0.83；单侧P = 0.231）为17.0周；多西他赛组（n = 41）为12周。三个治疗组的总生存期无统计学显著差异。常见不良事件包括腹泻、皮疹以及校正QT（QTC）间期的无症状延长。
达到了主要目标，与多西他赛相比，凡德他尼100mg联合多西他赛在预设显著性水平上显著延长了PFS。基于这些令人鼓舞的数据，已启动凡德他尼100mg联合多西他赛用于二线NSCLC的III期评估。
