Respiratory Oncology Unit, Department of Respiratory Medicine, University Hospitals KU Leuven, Leuven, Belgium
Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University-Assistance Publique Hôpitaux de Marseille, Marseille, France.
Ann Oncol. 2015 Aug;26(8):1734-40. doi: 10.1093/annonc/mdv219. Epub 2015 May 4.
This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC).
Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200.
There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator.
The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.
NCT00842712.
这项多中心、开放标签、随机、对照的 II 期研究评估了西利单抗联合西妥昔单抗和铂类化疗与西妥昔单抗和化疗单独用于晚期非小细胞肺癌（NSCLC）患者的一线治疗。
患者按 1:1:1 随机分为接受西妥昔单抗联合铂类化疗（对照组），或联合西利单抗 2000mg/周（CIL-once）或 2 周（CIL-twice）静脉滴注。一项方案修正案限制了纳入具有表皮生长因子受体（EGFR）组织评分≥200 的患者，并出于实际可行性问题关闭了 CIL-twice 臂。主要终点是无进展生存期（PFS；独立阅读）；次要终点包括总生存期（OS）、安全性和生物标志物分析。报告了 CIL-once 与对照组之间的比较，包括总队列和 EGFR 组织评分≥200 的患者。
CIL-once 组有 85 例患者，对照组有 84 例患者。CIL-once 与对照组的 PFS（独立阅读）分别为 6.2 个月和 5.0 个月[风险比（HR）0.72；P=0.085]；对于 EGFR 组织评分≥200 的患者，PFS 分别为 6.8 个月和 5.6 个月（HR 0.57；P=0.0446）。CIL-once 的中位 OS 为 13.6 个月，对照组为 9.7 个月（HR 0.81；P=0.265）。对于 EGFR≥200 的患者，OS 分别为 13.2 个月和 11.8 个月（HR 0.95；P=0.855）。CIL-once 与对照组之间报告的不良事件无重大差异；恶心（分别为 59%和 56%）和中性粒细胞减少（分别为 54%和 46%）是最常见的。西利单抗治疗患者的血栓栓塞事件或出血发生率没有增加。αvβ3 和 αvβ5 的表达既不是预测指标，也不是预后指标。
西利单抗联合西妥昔单抗/化疗显示出有潜力的临床活性，在独立阅读分析中显示出 PFS 差异的趋势。然而，观察到终点之间的不一致表明需要进一步研究以证实其他整合素抑制剂在 NSCLC 治疗中的潜在作用。
NCT00842712。
