A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer
A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer
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DOI：
10.1093/annonc/mdq731
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发表时间：
2011-09-01
影响因子：
50.5
通讯作者：
Schwartzberg, L.
中科院分区：
文献类型：
--
作者：
Blumenschein, G. R., Jr.;Kabbinavar, F.;Schwartzberg, L.
背景：这项II期研究评估了接受紫杉醇-卡铂(CP)联合莫替沙尼或贝伐单抗的晚期非小细胞肺癌(NSCLC)患者的客观缓解率(ORR)的差异。患者和方法：未接受化疗的患者(N=186)被随机分为三组，分别接受CP加莫替沙尼125 mg每日一次(A组)、莫替沙尼75 mg每日两次(B组)或贝伐单抗15 mg/kg每3周一次(Q3w)(C组)。主要终点是ORR(根据RECIST)。结果：A组的ORR为30%(95%可信区间为18%~43%)，B组为23%(13%~36%)，C组为37%(25%~50%)。中位PFS：A组为7.7个月，B组为5.8个月，C组为8.3个月，OS组为14.0个月，B组为12.8个月，C组为14.0个月。A组和B组AEs发生率高于C组(n=10)，B组(n=10)AEs发生率高于A组(n=4)和C组(n=4)。莫替沙尼的血浆C-max和C-min值与以往研究中观察到的药代动力学特性一致。结论：125 mg每日1次的莫替沙尼或贝伐单抗与CP的疗效相当。两支莫替沙尼的毒性都较高，但可控。莫他尼布125 mg，qd加CP治疗晚期非鳞状细胞肺癌的疗效和耐受性正在III期研究中进一步研究。
Background: This phase II study estimated the difference in objective response rate (ORR) among patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) receiving paclitaxel-carboplatin (CP) plus motesanib or bevacizumab.Patients and methods: Chemotherapy-naive patients (N = 186) were randomized 1: 1: 1 to receive CP plus motesanib 125 mg once daily (qd) (arm A), motesanib 75 mg twice daily (b.i.d.) 5 days on/2 days off (arm B), or bevacizumab 15 mg/kg every 3 weeks (q3w) (arm C). The primary end point was ORR (per RECIST). Other end points included progression-free survival (PFS), overall survival (OS), motesanib pharmacokinetics, and adverse events (AEs).Results: ORRs in the three arms were as follows: arm A, 30% (95% confidence interval 18% to 43%); arm B, 23% (13% to 36%); and arm C, 37% (25% to 50%). Median PFS in arm A was 7.7 months, arm B 5.8 months, and arm C 8.3 months; median OS for arm A was 14.0 months, arm B 12.8 months, and arm C 14.0 months. Incidence of AEs was greater in arms A and B than in arm C. More grade 5 AEs not attributable to disease progression occurred in arm B (n = 10) than in arms A (n = 4) and C (n = 4). Motesanib plasma C-max and C-min values were consistent with its pharmacokinetic properties observed in previous studies.Conclusions: The efficacy of 125 mg qd motesanib or bevacizumab plus CP was estimated to be comparable. Toxicity was higher but manageable in both motesanib arms. Efficacy and tolerability of motesanib 125 mg qd plus CP in advanced nonsquamous NSCLC are being further investigated in a phase III study.