既往接受过治疗的晚期非小细胞肺癌患者中阿帕替尼单药治疗的基因变异与疗效之间的关联：一项真实世界回顾性研究
Association Between Genetic Variation and Efficacy of Apatinib Monotherapy in Patients with Previously Treated Advanced NSCLC: A Real-World Retrospective Study.
作者信息
Hu Wenxia, Li Bin, Geng Nan, He Xin, Ge Hui, Wang Ping, Ding Cuimin
机构信息
Department of Respiratory Medicine, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, People's Republic of China.
出版信息
Int J Gen Med. 2021 Jun 21;14:2703-2714. doi: 10.2147/IJGM.S303717. eCollection 2021.
BACKGROUND
This study aimed to explore associations between polymorphisms and efficacy of apatinib for patients with previously treated advanced non-small cell lung cancer (NSCLC) in a real-world setting.
METHODS
We retrospectively recruited 148 patients with previously treated advanced NSCLC from January 2015 to December 2019 continuously. Clinical efficacy in patients receiving apatinib treatment was evaluated. Adverse reactions were documented during treatment. Biological specimens of peripheral blood and cancer tissue biopsies were obtained for the genotyping of genetic variations in and corresponding gene-mRNA expression, respectively. Univariate association analysis between the status of genetic variations and survival was performed with Kaplan-Meier survival analysis.
RESULTS
The objective response rate of the 148 patients was 17.6% and disease-control rate 68.9%. Prognostic data suggested that median progression-free survival (PFS) was 3.8 (95% CI 3.13-4.47) months and median overall survival (OS) 10.5 (95% CI 9.06-11.95) months. Regarding genetic variation, only rs2297136 was of clinical significance. Prognosis analysis revealed that PFS and OS for the rs2297136 genotype were significantly different. Median PFS of patients with TC/CC and TT genotypes was 3 and 4.5 months, respectively (=0.006). Median OS of the two genotypes was 9 and 11.6 months, respectively (=0.04). Furthermore, the safety profile suggested that the most common adverse reactions were hypertension, dermal toxicity, fatigue, and oral toxicity. This study failed to find any significant association between adverse reactions and rs2297136. Interestingly, mRNA-expression analysis demonstrated that mRNA expression of in biopsy cancer-tissue specimens was significantly different based on rs2297136-genotype status (<0.001).
CONCLUSION
polymorphism rs2297136 could be used as a potential biomarker for the prognosis of patients with NSCLC receiving apatinib monotherapy.
背景
本研究旨在探讨在真实世界中，多态性与阿帕替尼对既往接受过治疗的晚期非小细胞肺癌（NSCLC）患者疗效之间的关联。
方法
我们回顾性连续招募了2015年1月至2019年12月期间既往接受过治疗的148例晚期NSCLC患者。评估接受阿帕替尼治疗患者的临床疗效。记录治疗期间的不良反应。分别获取外周血和癌组织活检的生物标本，用于进行基因变异的基因分型和相应基因的mRNA表达。采用Kaplan-Meier生存分析对基因变异状态与生存之间进行单因素关联分析。
结果
148例患者的客观缓解率为17.6%，疾病控制率为68.9%。预后数据显示，中位无进展生存期（PFS）为3.8（95%CI 3.13 - 4.47）个月，中位总生存期（OS）为10.5（95%CI 9.06 - 11.95）个月。关于基因变异，只有rs2297136具有临床意义。预后分析显示，rs2297136基因型的PFS和OS有显著差异。TC/CC和TT基因型患者的中位PFS分别为3个月和4.5个月（P = 0.006）。两种基因型的中位OS分别为9个月和11.6个月（P = 0.04）。此外，安全性分析表明，最常见的不良反应为高血压、皮肤毒性、疲劳和口腔毒性。本研究未发现不良反应与rs2297136之间存在任何显著关联。有趣的是，mRNA表达分析表明，基于rs2297136基因型状态，活检癌组织标本中的mRNA表达存在显著差异（P < 0.001）。
结论
基因多态性rs2297136可作为接受阿帕替尼单药治疗的NSCLC患者预后的潜在生物标志物。
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