Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non-Small-Cell Lung Cancer
Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2010.32.8971
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发表时间：
2011-07-01
影响因子：
45.3
通讯作者：
Schiller, Joan H.
中科院分区：
文献类型：
--
作者：
Hirsh, Vera;Paz-Ares, Luis;Schiller, Joan H.
目的：本III期研究考察了合成toll样受体9激活寡脱氧核苷酸PF-3512676联合标准紫杉醇/卡铂化疗治疗晚期非小细胞肺癌（NSCLC）患者的疗效。IIIB期或IV期非小细胞肺癌患者被随机分配（1:1）接受最多6个疗程的紫杉醇/卡铂（静脉注射紫杉醇200 mg/m(2)和卡铂在3周周期的第1天在[浓度-时间]曲线下的区域6）单独（对照组）或在第8天和第15天联合0.2 mg/kg皮下PF-3512676（研究组）。主要终点为总生存期（OS）。结果各组基线人口统计学相似（N = 828）。大多数患者（88%）为IV期疾病。中位OS和中位无进展生存期（PFS）相似（OS：研究组，10.0个月vs对照组，9.8个月；P = 0.56； PFS：研究组，4.8个月vs对照组，4.7个月；P = 0.79）。最常报道的pf -3512676相关不良事件（ae）是轻度至中度局部注射部位反应、发热和流感样症状。在研究组中，3 - 4级不良事件（包括中性粒细胞减少症、血小板减少症和贫血）更为频繁，与对照组相比，更多的患者有一种或多种与败血症相关的不良事件（17 vs 3）。在最初的中期分析中，数据安全监测委员会建议停止研究，因为在PF-3512676组中缺乏增加的疗效和更多与败血症相关的严重ae。停止给药PF-3512676，但不停止化疗。结论与单用紫杉醇/卡铂相比，在一线治疗晚期NSCLC患者时，PF-3512676联合紫杉醇/卡铂并没有改善OS或PFS，但却增加了毒性。该方案不推荐用于治疗晚期非小细胞肺癌患者。[J]中华医学杂志，29(2):667- 674。(C) 2011年美国临床肿瘤学会
PurposeThis phase III study examined efficacy of the synthetic Toll-like receptor 9-activating oligodeoxy-nucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1: 1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m(2) and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS).ResultsBaseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676-related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted.ConclusionAddition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC. J Clin Oncol 29:2667-2674. (C) 2011 by American Society of Clinical Oncology