Heymach John V, Paz-Ares Luis, De Braud Filippo, Sebastian Martin, Stewart David J, Eberhardt Wilfried E E, Ranade Anantbhushan A, Cohen Graham, Trigo Jose Manuel, Sandler Alan B, Bonomi Philip D, Herbst Roy S, Krebs Annetta D, Vasselli James, Johnson Bruce E
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Clin Oncol. 2008 Nov 20;26(33):5407-15. doi: 10.1200/JCO.2008.17.3138. Epub 2008 Oct 20.
Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC).
All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment.
The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention.
VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
凡德他尼是一种每日一次的口服血管内皮生长因子受体和表皮生长因子受体信号传导抑制剂。在既往未接受过治疗的非小细胞肺癌（NSCLC）患者中，比较了凡德他尼单药治疗或凡德他尼联合紫杉醇和卡铂（VPC）与紫杉醇和卡铂（PC）的抗肿瘤活性。
在这项部分盲法、安慰剂对照、随机II期研究中，允许纳入所有NSCLC组织学类型以及既往有中枢神经系统转移的患者。患者按2:1:1随机分组，分别接受凡德他尼、VPC或PC治疗。无进展生存期（PFS）是主要终点，该研究旨在检测VPC与PC相比进展风险降低（风险比=0.70；单侧P<0.2），并证明凡德他尼与PC相比不劣效。总生存期是次要评估指标。
与接受PC治疗的患者（n = 52；风险比=0.76，单侧P = 0.098）相比，接受VPC治疗的患者（n = 56）进展风险降低；中位PFS为24周（VPC）和23周（PC）。在计划的中期PFS分析达到停药标准（风险比>1.33对比PC）后，凡德他尼单药治疗组（n = 73）停止治疗。接受VPC或PC治疗的患者总生存期无显著差异。皮疹、腹泻和高血压是常见不良事件；无需干预肺或中枢神经系统出血事件。
VPC可安全用于NSCLC患者，包括鳞状细胞组织学类型和有脑转移的患者。与PC对照组相比，接受VPC治疗的患者PFS更长，达到了预先设定的研究终点，而接受凡德他尼单药治疗的患者PFS更短。
