安罗替尼单药治疗89例老年广泛期小细胞肺癌的疗效和安全性分析

Efficacy and Safety of Anlotinib Monotherapy for 89 Elderly Patients with Extensive-stage Small Cell Lung Cancer

[目的]探讨老年广泛期小细胞肺癌(extensive-stage small cell lung cancer,ES-SCLC)患者接受安罗替尼单药治疗的疗效和安全性,同时分析高血压与预后的关联性。[方法]本研究设计为回顾性分析,共纳入89例60岁以上的经标准方案治疗失败的ES-SCLC患者,接受起始剂量为12 mg或10 mg的安罗替尼单药治疗。通过电子病历系统收集患者的基本人口学资料、治疗的疗效数据,生存预后及不良反应。采用Kaplan-Meier生存曲线进行无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS)分析,并通过Cox回归进行多因素分析。本研究的主要研究终点为PFS,次要研究终点为客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、OS、安全性。[结果]89例老年ES-SCLC患者经过安罗替尼治疗后部分缓解5例,疾病稳定64例,疾病进展20例。安罗替尼单药治疗老年ES-SCLC患者的ORR为5.6%(95%CI:1.85%~12.63%),DCR为77.5%(95%CI:67.45%~85.70%)。89例老年患者的中位PFS为3.3个月(95%CI:2.63~3.97),中位OS为7.3个月(95%CI:5.97~8.63)。安罗替尼单药治疗的老年患者常见的不良反应有高血压、手足皮肤反应、疲劳、纳差、蛋白尿和血液学毒性等。出现高血压患者31例。高血压是影响PFS的独立因素(HR=0.71,P=0.024)。[结论]安罗替尼在标准方案治疗失败的老年ES-SCLC患者具有初步的疗效及可耐受的安全性。安罗替尼治疗过程中出现的高血压可作为预测PFS的指标。

[Objective]To investigate the efficacy and safety of anlotinib monotherapy for elderly patients with extensive-stage small cell lung cancer(ES-SCLC)and to explore the association between hypertension status and prognosis simultaneously.[Methods]Designed as a retrospective analysis,this study included a total of 89 elderly patients with ES-SCLC over 60 years old who failed after the standard regimens.All the subjects were treated with anlotinib monotherapy at an initial dosage of 12 mg or 10 mg.Clinical and demographic characteristics of the elderly patients were collected through the medical records of the patients in the department and the electronic medical record system in the hospital.Follow-up was performed and toxicity profile was recorded,respectively.Progression free survival(PFS)and overall survival(OS)were carried out with Kaplan-Meier survival curves and multivariate analysis were adjusted by Cox regression analysis.The primary endpoint was PFS,the secondary endpoints were objective response rate(ORR),disease control rate(DCR),OS,safety profile and the association analysis between hypertension status and prognosis.[Results]The best overall response of the 89 elderly patients with ES-SCLC receiving anlotinib monotherapy suggested that partial response was observed in 5 patients,stable disease was noted in 64 patients and progressive disease was seen in 20 patients.Therefore,the ORR of anlotinib in elderly patients with ES-SCLC was 5.6%(95%CI:1.85%~12.63%),DCR was 77.5%(95%CI:67.45%~85.70%).The median PFS of the 89 elderly patients with ES-SCLC was 3.3 months(95%CI:2.63~3.97),the median OS was 7.3 months(95%CI:5.97~8.63).The toxicity profile demonstrated that the most common adverse reactions of elderly patients receiving anlotinib monotherapy were hypertension,hand-foot syndrome,fatigue,anorexia,proteinuria and hematological toxicity.Among them,a total of 31 patients developed hypertension.Additionally,Cox multivariate analysis for PFS demonstrated that hypertension status was an independent factor for PFS(HR=0.71,P=0.024).[Conclusion]Anlotinib was of potential efficacy and tolerable safety for elderly patients with ES-SCLC who failed after the standard regimens.Hypertension that occurred in the treatment of anlotinib might serve as a useful biomarker to predict PFS.