Zhang Limin, Jiang Tao, Li Xuefei, Wang Yan, Zhao Chao, Zhao Sha, Xi Lei, Zhang Shijia, Liu Xiaozhen, Jia Yijun, Yang Hui, Shi Jinpeng, Su Chunxia, Ren Shengxiang, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Cancer. 2017 Aug 1;123(15):2927-2935. doi: 10.1002/cncr.30677. Epub 2017 Mar 27.
The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib.
A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study. The Bim deletion polymorphism was analyzed by polymerase chain reaction. The clinical features of the Bim deletion polymorphism and its impact on the effect of crizotinib were investigated.
The Bim deletion polymorphism was present in 9 of 69 patients with ALK-positive or ROS1-positive NSCLC (13.0%). There were no differences noted with regard to clinicopathological features between patients with and without the Bim deletion polymorphism. Patients with the Bim deletion polymorphism had a significantly shorter progression-free survival (PFS) and lower objective response rate compared with those without (median PFS, 182 days vs 377 days [P = .008]) (objective response rate, 44.4% vs 81.7% [P =.041]) in all populations. The significant difference in PFS was observed in patients with ALK-positive NSCLC (83 days vs 305 days [P =.0304]) compared with those with ROS1-positive NSCLC (218 days vs not reached [P =.082]). Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]).
The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC. Cancer 2017;123:2927-35. © 2017 American Cancer Society.
作者之前的研究表明，B细胞慢性淋巴细胞白血病/淋巴瘤（Bcl-2）样11（BCL2L11）（Bim）缺失多态性与表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者对EGFR酪氨酸激酶抑制剂的临床反应不佳相关。本研究的目的是调查Bim缺失多态性对接受克唑替尼治疗的间变性淋巴瘤激酶（ALK）阳性或ROS原癌基因1、受体酪氨酸激酶（ROS1）阳性NSCLC患者的影响。
共有55例接受克唑替尼治疗的ALK阳性NSCLC患者和14例ROS1阳性NSCLC患者纳入本研究。通过聚合酶链反应分析Bim缺失多态性。研究Bim缺失多态性的临床特征及其对克唑替尼疗效的影响。
69例ALK阳性或ROS1阳性NSCLC患者中有9例存在Bim缺失多态性（13.0%）。有或无Bim缺失多态性的患者在临床病理特征方面无差异。在所有人群中，与无Bim缺失多态性的患者相比，有该多态性的患者无进展生存期（PFS）显著缩短，客观缓解率更低（中位PFS，182天对377天[P = 0.008]）（客观缓解率，44.4%对81.7%[P = 0.041]）。与ROS1阳性NSCLC患者（218天对未达到[P = 0.082]）相比，ALK阳性NSCLC患者的PFS有显著差异（83天对305天[P = 0.0304]）。多因素分析表明，Bim缺失多态性是接受克唑替尼治疗的ALK阳性NSCLC患者的独立预测因素（风险比，4.786[P = 0.006]）。
发现Bim缺失多态性与ALK融合阳性NSCLC患者对克唑替尼的临床反应不佳相关。《癌症》2017年；123：2927 - 35。©2017美国癌症协会。
