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晚期非小细胞肺癌(NSCLC)抗血管生成治疗的最新进展。

Update on antiangiogenic treatment of advanced non-small cell lung cancer (NSCLC).

机构信息

Interdisciplinary Thoracic Oncology, Department of Surgery, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

出版信息

Target Oncol. 2013 Mar;8(1):15-26. doi: 10.1007/s11523-013-0261-1. Epub 2013 Feb 1.

Abstract

Bevacizumab is a monoclonal antibody that specifically inhibits vascular endothelial growth factor, and is the first antiangiogenic agent to be approved for first-line treatment of advanced non-small cell lung cancer (NSCLC). Evidence from two large phase III trials demonstrates that bevacizumab combined with chemotherapy improves outcomes for patients with non-squamous NSCLC. In patients with adenocarcinoma without epidermal growth factor receptor (EGFR) mutation, a median overall survival of 18.0 months is achieved. Several post-registration phase IV studies have confirmed bevacizumab's efficacy and tolerability profile and have clarified the eligibility criteria. Clinical research is still ongoing to define the role of bevacizumab in different settings, such as single-agent bevacizumab for continuation maintenance therapy in advanced disease, treatment beyond disease progression, adjuvant therapy in early-stage NSCLC, or bevacizumab in combination with other targeted agents. A number of antiangiogenic tyrosine kinase inhibitors (TKI) have also been investigated in phase II and III trials. None of these drugs has proven significant clinical benefit in unselected patient populations. This article reviews the extensive information from randomized trials and large observational studies for bevacizumab in advanced NSCLC, and shortly describes the current clinical development of antiangiogenic monoclonal antibodies, TKIs and related compounds.

摘要

贝伐珠单抗是一种单克隆抗体,特异性抑制血管内皮生长因子,是第一个被批准用于晚期非小细胞肺癌(NSCLC)一线治疗的抗血管生成药物。两项大型 III 期临床试验的证据表明,贝伐珠单抗联合化疗可改善非鳞状 NSCLC 患者的结局。对于无表皮生长因子受体(EGFR)突变的腺癌患者,中位总生存期达到 18.0 个月。几项上市后 IV 期研究证实了贝伐珠单抗的疗效和耐受性,并明确了入选标准。临床研究仍在进行中,以确定贝伐珠单抗在不同情况下的作用,例如单药贝伐珠单抗用于晚期疾病的持续维持治疗、疾病进展后的治疗、早期 NSCLC 的辅助治疗或与其他靶向药物联合使用。一些抗血管生成的酪氨酸激酶抑制剂(TKI)也已在 II 期和 III 期试验中进行了研究。这些药物在未经选择的患者人群中均未证明具有显著的临床获益。本文综述了晚期 NSCLC 贝伐珠单抗的随机试验和大型观察性研究的大量信息,并简要描述了抗血管生成单克隆抗体、TKI 及相关化合物的当前临床开发情况。

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