Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial.
Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial.
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DOI：
10.1016/s1470-2045(10)70132-7
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发表时间：
2010-07
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通讯作者：
Johnson BE
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作者：
Herbst RS;Sun Y;Eberhardt WE;Germonpré P;Saijo N;Zhou C;Wang J;Li L;Kabbinavar F;Ichinose Y;Qin S;Zhang L;Biesma B;Heymach JV;Langmuir P;Kennedy SJ;Tada H;Johnson BE
凡德他尼是一种每日一次的口服血管内皮生长因子受体、表皮生长因子受体以及转染重排（RET）酪氨酸激酶抑制剂。在一项针对既往接受过治疗的非小细胞肺癌（NSCLC）患者的2期随机研究中，与单独使用多西他赛相比，添加100mg凡德他尼至多西他赛显著改善了无进展生存期（PFS），包括女性患者的无进展生存期更长。这些结果支持在这项更大规模的、确定性的3期试验（ZODIAC）中对该联合用药进行研究。
2006年5月至2008年4月期间，一线化疗后进展的局部晚期或转移性（IIIB - IV期）非小细胞肺癌患者通过第三方交互式语音系统按1∶1随机分配，接受凡德他尼（100mg/天）加多西他赛（每21天静脉注射75mg/m²；最多六个周期）或安慰剂加多西他赛。主要目的是在意向性治疗人群中比较两组之间的无进展生存期。女性是共同主要分析人群。该研究已完成，并在ClinicalTrials.gov注册，注册号为NCT00312377。
1391名患者接受了凡德他尼加多西他赛（n = 694[197名女性]）或安慰剂加多西他赛（n = 697[224名女性]）。与单独使用多西他赛相比，凡德他尼加多西他赛显著改善了无进展生存期（风险比[HR]0.79，97.58%置信区间0.70 - 0.90；p < 0.0001）；凡德他尼组的中位无进展生存期为4.0个月，而安慰剂组为3.2个月。在女性中，凡德他尼加多西他赛与安慰剂加多西他赛相比，无进展生存期也有类似改善（HR 0.79，0.62 - 1.00，p = 0.024）；凡德他尼组的中位无进展生存期为4.6个月，而安慰剂组为4.2个月。在3级或更高级别的不良事件中，皮疹（63/689[9%]对7/690[1%]）、中性粒细胞减少症（199/689[29%]对164/690[24%]）和发热性中性粒细胞减少症（61/689[9%]对48/690[7%]）在凡德他尼加多西他赛组比安慰剂加多西他赛组更常见。最常见的严重不良事件是发热性中性粒细胞减少症（凡德他尼组46/689[7%]，安慰剂组38/690[6%]）。
在一线治疗后进展的晚期非小细胞肺癌患者中，多西他赛添加凡德他尼可显著改善无进展生存期。
阿斯利康
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC). Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB–IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 IV every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov, number NCT00312377. 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus docetaxel alone (hazard ratio [HR] 0·79, 97·58% CI 0·70–0·90; p<0·0001); median PFS was 4·0 months in the vandetanib group versus 3·2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0·79, 0·62–1·00, p=0·024); median PFS was 4·6 months in the vandetanib group versus 4·2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel than with placebo plus docetaxel. The most common serious adverse event was febrile neutropenia (46/689 [7%] in the vandetanib group vs 38/690 [6%] in the placebo group). The addition of vandetanib to docetaxel provides a significant improvement in PFS in patients with advanced NSCLC after progression following first-line therapy. AstraZeneca.