Western Hospital, Melbourne, Australia.
J Clin Oncol. 2011 Mar 10;29(8):1067-74. doi: 10.1200/JCO.2010.29.5717. Epub 2011 Jan 31.
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non-small-cell lung cancer.
Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments.
There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed.
This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.
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抑制剂。这项随机、安慰剂对照的 III 期研究评估了凡德他尼联合培美曲塞作为晚期非小细胞肺癌二线治疗的疗效。
患者（N=534）随机分为凡德他尼 100mg/d 联合培美曲塞 500mg/m²，每 21 天一次（n=256）或安慰剂联合培美曲塞（n=278）。无进展生存期（PFS）是主要终点；总生存期、客观缓解率、疾病控制率、症状恶化时间和安全性是次要评估指标。
治疗组之间的 PFS 无显著差异（风险比[HR]，0.86；97.58%CI，0.69 至 1.06；P=0.108）。总生存期也无显著差异（HR，0.86；97.54%CI，0.65 至 1.13；P=0.219）。凡德他尼组客观缓解率（19%比 8%；P<0.001）和症状恶化时间（HR，0.71；P=0.0052；中位数，凡德他尼组为 18.1 周，安慰剂组为 12.1 周）有显著改善。与安慰剂组相比，培美曲塞联合凡德他尼增加了皮疹、腹泻和高血压等一些不良反应的发生率，同时降低了恶心、呕吐、贫血、疲劳和乏力的发生率，而培美曲塞的剂量强度没有降低。
本研究未达到主要终点，即与安慰剂加培美曲塞相比，凡德他尼加培美曲塞治疗不能显著延长 PFS。与安慰剂组相比，凡德他尼联合培美曲塞组的客观缓解率显著提高，肺癌症状恶化时间显著延迟，且在该患者人群中具有可接受的安全性。
