University of Turin, S. Luigi Hospital, Turin, Italy.
J Clin Oncol. 2012 Aug 10;30(23):2829-36. doi: 10.1200/JCO.2011.41.4987. Epub 2012 Jul 2.
We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non-small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma.
Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS.
A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment.
Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
我们评估了莫特塞尼布（一种选择性的口服血管内皮生长因子受体 1、2 和 3、血小板衍生生长因子受体和 Kit 的抑制剂）与卡铂/紫杉醇联合应用是否能改善非鳞状非小细胞肺癌（NSCLC）患者，特别是腺癌患者的总生存期（OS），与单纯化疗相比。
IIIb/IV 期或复发性非鳞状 NSCLC（无晚期疾病的既往系统治疗）患者以 1:1 的比例随机分配，接受卡铂（曲线下面积，6mg/ml·min）和紫杉醇（200mg/m2）静脉滴注，最多 6 个 3 周周期，同时每天口服莫特塞尼布 125mg（A 组）或安慰剂（B 组）。OS 是主要终点。次要终点包括无进展生存期（PFS）、客观缓解率（ORR）、不良事件（AE）以及胎盘生长因子（PLGF）变化与 OS 的关系。
共 1090 例非鳞状 NSCLC 患者被随机分配（A 组/B 组，549 例中的 541 例）；其中 890 例为腺癌（442 例中的 448 例）。A 组和 B 组的中位 OS 分别为 13.0 和 11.0 个月（HR，0.90；95%CI，0.78 至 1.04；P=0.14）；腺癌亚组的中位 OS 分别为 13.5 和 11.0 个月（HR，0.88；95%CI，0.75 至 1.03；P=0.11）。在描述性分析（A 组与 B 组）中，中位 PFS 分别为 5.6 个月和 5.4 个月（P<0.001）；ORR 分别为 40%和 26%（P<0.001）。A 组中 PLGF 变化与 OS 之间无相关性。莫特塞尼布治疗的不良反应发生率（A 组和 B 组分别为 73%和 59%）和 5 级不良反应发生率（A 组和 B 组分别为 14%和 9%）均较高。
莫特塞尼布联合卡铂/紫杉醇与单纯卡铂/紫杉醇相比，并未显著改善晚期非鳞状 NSCLC 患者或腺癌亚组患者的 OS。
