安罗替尼单药治疗多线治疗进展后晚期肺癌伴脑转移的疗效、安全性观察及Kaplan-Meier生存分析

Efficacy,safety and Kaplan-Meier survival analysis of Anlotinib monotherapy for advanced lung cancer with brain metastasis after multi-line therapy progresses

目的探讨安罗替尼单药应用于多线治疗出现进展后晚期肺癌伴脑转移患者的临床疗效、安全性观察及Kaplan-Meier生存分析。方法前瞻性选取2018年9月至2020年1月于池州市人民医院肿瘤科病理确诊的Ⅳ期、既往接受三线及以上治疗方案的肺癌伴脑转移患者27例,予以安罗替尼口服治疗。观察并记录患者无进展生存时间(PFS)、颅内无进展生存时间(iPFS)、客观缓解率(ORR)、疾病控制率(DCR)、颅内客观缓解率(iORR)和安全性。采用Cox多因素分析患者PFS和iPFS的影响。观察服用安罗替尼后不良事件。结果本研究27例患者疗效评估,完全缓解0例,部分缓解14例,疾病稳定9例,疾病进展4例;ORR 51.85%,DCR 85.18%。脑转移评估,完全缓解0例,部分缓解17例,疾病稳定7例,疾病进展3例;iORR 62.96%。患者中位PFS和iPFS分别为3.20个月(95%CI:2.62-3.78个月)和3.70个月(95%CI:2.82-4.58个月)。单因素分析,肺癌伴脑转移患者性别、年龄、病例类型、吸烟史、脑转移症状、安罗替尼治疗线数、EGFR突变、EGFR-TKI治疗、脑放疗对患者PFS及iPFS无显著影响(P>0.05)。其中ECOG评分对患者PFS及iPFS有关(P<0.05)。多因素分析提示ECOG评分、脑转移症状、安罗替尼治疗线数、EGFR突变、EGFR-TKI治疗、EGFR-TKI治疗对肺癌伴脑转移患者PFS及iPFS具有显著影响(P<0.05)。所有患者未出现3-4级不良反应事件,常见不良反应为口腔黏膜炎、高血压、疲劳等均为1-2级,患者未出现咳血以及颅内出血等严重不良反应。结论安罗替尼单药对多线治疗进展后的肺癌伴脑转移具有良好的疾病控制率,并在一定程度上延长患者的生存期,但受ECOG评分、脑转移症状、安罗替尼治疗线数等因素影响,且不良反应耐受性较好,具有一定的临床应用价值。

Objective To investigate the efficacy,safety and Kaplan-Meier survival analysis of Anlotinib monotherapy for advanced lung cancer with brain metastases after multi-line therapy progresses.Methods Twenty-seven patients with lung cancer and brain metastases who had been diagnosed in stageⅣand previously received third-line and above treatment options in Department Oncology,Chizhou People's Hospital from September 2018 to January 2020 were selected for oral treatment with Anlotinib.The patient's progression-free survival time(PFS),intracranial progression-free survival time(iPFS),objective response rate(ORR),disease control rate(DCR),intracranial objective response rate(iORR)and safety were observed and recorded.The effects of patient PFS and iPFS were analyzed using Cox multivariate.Adverse events were observed after taking anlotinib.Results The efficacy evaluation of 27 patients in this study included complete remission in 0 cases,partial remission in 14 cases,stable disease in 9 cases,and disease progression in 4 cases,ORR was 51.85%,and DCR was 85.18%.Evaluation of brain metastasis included complete remission in 0 cases,partial remission in 17 cases,stable disease in 7 cases,disease progression in 3 cases.The iORR was 62.96%.The median PFS and iPFS of the patients were 3.20 months(95%CI:2.62-3.78 months)and 3.70 months(95%CI:2.82-4.58 months),respectively.According to univariate analysis,gender,age,case type,smoking history,brain metastasis symptoms,treatment lines of Anlotinib,EGFR mutation,EGFR-TKI treatment,and brain radiotherapy in patients with lung cancer with brain metastasis had no significant effect on PFS and iPFS(P>0.05).Among them,ECOG score was related to PFS and iPFS of patients(P<0.05).Multivariate analysis showed that ECOG score,brain metastasis symptoms,treatment lines of Anlotinib,EGFR mutation,EGFR-TKI treatment,and EGFR-TKI treatment had a significant impact on PFS and iPFS in patients with lung cancer and brain metastases(P<0.05).All patients did not experience grade 3-4 adverse events.Common adverse reactions were oral mucositis,hypertension,fatigue,etc.in all grade 1 to 2.The patient had no serious adverse reactions such as hemoptysis and intracranial hemorrhage.Conclusion Single Anlotinib has a good disease control rate for lung cancer with brain metastasis after multi-line treatment progresses,and prolongs the patient's survival to a certain extent,and the adverse reactions are well tolerated,and it has a certain clinical application value.