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非小细胞肺癌和小细胞肺癌治疗的最新进展。

Recent advances in the treatment of non-small cell and small cell lung cancer.

作者信息

Stinchcombe Thomas E

机构信息

University of North Carolina at Chapel Hill 170 Manning Drive, Physician's Office Building, 3rd Floor, Chapel Hill, NC 27599-7305 USA.

出版信息

F1000Prime Rep. 2014 Dec 1;6:117. doi: 10.12703/P6-117. eCollection 2014.

Abstract

Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival.

摘要

2014年5月30日至6月3日在美国临床肿瘤学会(ASCO)会议上展示的最新报告,将对非小细胞肺癌(NSCLC)和广泛期小细胞肺癌(ES-SCLC)的常规临床护理及临床试验发展产生影响。具有激活型表皮生长因子受体(EGFR)突变(定义为外显子19和外显子21 L858R点突变)的患者,使用EGFR酪氨酸激酶抑制剂时会有较高的客观缓解率和延长的无进展生存期。然而,不可避免地,患者会出现疾病进展,获得性耐药的最常见机制是EGFR外显子20 T790M突变。几种药物(AZD9291、CO-1686和HM61713)已在具有T790M耐药突变的患者中显示出令人瞩目的活性。还展示了关于阿法替尼一线治疗以及厄洛替尼与贝伐单抗联合治疗EGFR突变NSCLC患者疗效的更多数据。在一线治疗中,克唑替尼与铂-培美曲塞对比的III期试验结果,以及色瑞替尼的I期试验和扩展队列,为间变性淋巴瘤激酶重排的NSCLC患者提供了更多疗效和毒性数据。顺铂和吉西他滨联合或不联合耐昔妥珠单抗的III期试验显示,在鳞状NSCLC患者中添加耐昔妥珠单抗可改善总生存期。在二线治疗中,多西他赛联合雷莫西尤单抗或安慰剂的III期试验显示,添加雷莫西尤单抗可改善总生存期。在广泛期小细胞肺癌中,巩固性胸部放疗和预防性颅脑放疗的III期试验未能显示总生存期有所改善。

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