Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou, 510080, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
BMC Cancer. 2018 Nov 26;18(1):1171. doi: 10.1186/s12885-018-5078-y.
Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI). The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression.
Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH. C-Met expression was performed by IHC in ALK-rearranged patients, and more than 50% of cells with high staining were defined as c-Met overexpression. The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression.
Sixteen patients were identified with c-Met overexpression in 160 ALK-rearranged cases, with the incidence of 10.0% (16/160). A total of 116 ALK-rearranged patients received the treatment of crizotinib. Objective response rate (ORR) was 86.7% (13/15) in ALK-rearranged patients with c-Met overexpression and 59.4% (60/101)in those without c-Met overexpression, P = 0.041. Median PFS showed a trend of superiority in c-Met overexpression group (15.2 versus 11.0 months, P = 0.263). Median overall survival (OS) showed a significant difference for ALK-rearranged patients with c-Met overexpression group of 33.5 months with the hazard ratio (HR) of 3.2.
C-Met overexpression co-exists with ALK rearrangement in a small population of advanced NSCLC. There may be a trend of favorable efficacy of crizotinib in such co-altered patients.
克唑替尼可靶向针对间质-上皮转化（MET）和间变性淋巴瘤激酶（ALK），已被认为是一种多靶点酪氨酸激酶抑制剂（TKI）。本研究旨在探索克唑替尼治疗同时伴有 ALK 重排和 c-Met 过表达的晚期非小细胞肺癌（NSCLC）的疗效。
本研究共纳入了来自两个机构的 4622 例晚期 NSCLC 患者（2011 年 1 月至 2016 年 12 月期间广东肺癌研究所的 3762 例患者和 2015 年 1 月至 2016 年 12 月期间北京肿瘤医院的 860 例患者），通过免疫组化（IHC）、套式逆转录聚合酶链反应（RACE-coupled PCR）或荧光原位杂交（FISH）等任何方法筛选 ALK 重排。在 ALK 重排的患者中通过 IHC 检测 c-Met 的表达，高染色的细胞超过 50%被定义为 c-Met 过表达。探索了克唑替尼在伴有或不伴有 c-Met 过表达的 ALK 重排患者中的疗效。
在 160 例 ALK 重排患者中发现了 16 例（10.0%，16/160）存在 c-Met 过表达。116 例 ALK 重排患者接受了克唑替尼治疗。c-Met 过表达组的客观缓解率（ORR）为 86.7%（13/15），无 c-Met 过表达组为 59.4%（60/101），两组之间差异有统计学意义（P=0.041）。c-Met 过表达组的中位无进展生存期（PFS）有优势趋势（15.2 个月比 11.0 个月，P=0.263）。c-Met 过表达组的中位总生存期（OS）为 33.5 个月，风险比（HR）为 3.2，与 ALK 重排患者的 OS 存在显著差异。
在一小部分晚期 NSCLC 患者中，c-Met 过表达与 ALK 重排共存。在这种共同改变的患者中，克唑替尼可能有良好的疗效趋势。
