随机、安慰剂对照、1b/2 期研究：利妥木单抗或根特木单抗联合铂类化疗作为广泛期小细胞肺癌一线治疗。
A Randomized, Placebo-Controlled, Phase 1b/2 Study of Rilotumumab or Ganitumab in Combination With Platinum-Based Chemotherapy as First-Line Treatment for Extensive-Stage Small-Cell Lung Cancer.
机构信息
The University of Texas MD Anderson Cancer Center, Houston, TX.
Gustave Roussy, Villejuif, and Paris-Sud University, Orsay, France.
出版信息
Clin Lung Cancer. 2017 Nov;18(6):615-625.e8. doi: 10.1016/j.cllc.2017.05.007. Epub 2017 May 10.
INTRODUCTION/BACKGROUND: In this randomized, double-blind, placebo-controlled phase 1b/2 study we assessed the efficacy/safety of rilotumumab or ganitumab combined with etoposide and carboplatin or cisplatin as first-line treatment in patients with extensive stage small-cell lung cancer (ES-SCLC).
PATIENTS AND METHODS
In the phase 1b study, patients received rilotumumab 15 mg/kg or ganitumab 18 mg/kg with etoposide and carboplatin or cisplatin. In the phase 2 study, patients were randomly assigned 1:1:1 to receive placebo, rilotumumab, or ganitumab with etoposide and carboplatin or cisplatin. Chemotherapy was administered for ≤ 6 cycles; rilotumumab, ganitumab, or placebo was then continued as maintenance therapy. The primary end points were incidence of dose-limiting toxicities (DLTs; phase 1b) and overall survival (OS; phase 2). Secondary end points included progression-free survival (PFS) and safety.
RESULTS
In the phase 1b study (n = 28), 1 patient treated with ganitumab experienced a DLT (Grade 4 neutropenia/thrombocytopenia lasting ≥ 7 days). In the phase 2 study, 185 patients were enrolled (placebo, n = 61; rilotumumab, n = 62; ganitumab, n = 62). Median OS was 10.8, 12.2 (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.56-1.25; P = .384), and 10.7 (HR, 0.95; 95% CI, 0.63-1.41; P = .787) months, in placebo, rilotumumab, or ganitumumab arms, respectively. Median PFS was 5.4, 5.4 (HR, 1.05; 95% CI, 0.71-1.54; P = .797), and 5.5 (HR, 1.05; 95% CI, 0.72-1.55; P = .780) months, respectively. Adverse events resulting in treatment discontinuation occurred in 11 (19%), 10 (16%), and 7 (12%) patients, respectively. Serum biomarker analysis showed improved survival for patients with baseline hepatocyte growth factor levels below the median in the rilotumumab arm.
CONCLUSION
Although the combination of rilotumumab or ganitumab with chemotherapy was tolerable, overall outcomes were not improved in patients with ES-SCLC.
简介/背景：在这项随机、双盲、安慰剂对照的 1b/2 期研究中，我们评估了利妥木单抗或根特昔单抗联合依托泊苷和卡铂或顺铂作为广泛期小细胞肺癌（ES-SCLC）患者一线治疗的疗效/安全性。
患者和方法
在 1b 期研究中，患者接受利妥木单抗 15mg/kg 或根特昔单抗 18mg/kg 联合依托泊苷和卡铂或顺铂。在 2 期研究中，患者以 1:1:1 的比例随机分配接受安慰剂、利妥木单抗或根特昔单抗联合依托泊苷和卡铂或顺铂。化疗最多进行 6 个周期；然后继续给予利妥木单抗、根特昔单抗或安慰剂作为维持治疗。主要终点是剂量限制毒性（DLT；1b 期）和总生存期（OS；2 期）的发生率。次要终点包括无进展生存期（PFS）和安全性。
结果
在 1b 期研究（n=28）中，1 名接受根特昔单抗治疗的患者出现 DLT（4 级中性粒细胞减少症/血小板减少症持续时间≥7 天）。在 2 期研究中，共纳入 185 名患者（安慰剂组 n=61；利妥木单抗组 n=62；根特昔单抗组 n=62）。安慰剂、利妥木单抗和根特昔单抗组的中位 OS 分别为 10.8、12.2（风险比[HR]，0.84；95%置信区间[CI]，0.56-1.25；P=0.384）和 10.7（HR，0.95；95% CI，0.63-1.41；P=0.787）个月。安慰剂、利妥木单抗和根特昔单抗组的中位 PFS 分别为 5.4、5.4（HR，1.05；95% CI，0.71-1.54；P=0.797）和 5.5（HR，1.05；95% CI，0.72-1.55；P=0.780）个月。分别有 11（19%）、10（16%）和 7（12%）名患者因治疗相关不良事件而停药。血清生物标志物分析显示，在利妥木单抗组中，基线肝细胞生长因子水平低于中位数的患者生存得到改善。
结论
尽管利妥木单抗或根特昔单抗联合化疗可耐受，但广泛期小细胞肺癌患者的总体预后并未改善。
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