恩沙替尼治疗ALK阳性非小细胞肺癌的真实世界临床安全性监测与评估

Analyzing and monitoring real-world clinical safety of ensartinib for the treatment of patients with ALK-positive non-small cell lung cancer

目的评价恩沙替尼治疗间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌(NSCLC)的真实世界临床用药安全性。方法收集2020年12月16日至2021年12月16日接受恩沙替尼治疗(225 mg/次,1次/d)的2221例ALK阳性局部晚期或转移性NSCLC患者临床资料,分析患者药物不良反应以及老年患者(年龄≥65岁)药物不良反应发生情况。结果2221例患者中511例(23.01%)发生不良反应,其中8例(0.36%)患者发生严重不良反应。67例(3.02%)患者因不良反应导致剂量调整,18例(0.81%)患者因不良反应导致停药。不良反应主要表现为皮疹(407/2221,18.33%)、瘙痒(41/2221,1.85%)、便秘(41/2221,1.85%)和面部水肿(31/2221,1.40%)。36例(1.62%)患者发生≥3级不良反应。511例发生不良反应患者经对症治疗后,50例(9.78%)痊愈,271例(53.03%)好转,120例(23.48%)持续原状,70例(13.71%)由于失访或其他原因转归情况不祥。43例(1.94%)患者报告了57例次的非预期不良反应。599例老年患者中116例(19.37%)发生不良反应,其中1例(0.17%)患者发生严重不良反应。25例(4.17%)患者因不良反应导致剂量调整,5例(0.83%)患者因不良反应导致停药。老年患者不良反应主要表现为皮疹(88/599,14.69%)、便秘(14/599,2.34%)、面部水肿(12/599,2.00%)和瘙痒(10/599,1.67%)。12例(2.00%)患者发生≥3级不良反应。116例发生不良反应的老年患者中经对症治疗后,11例(9.48%)痊愈,58例(50.00%)好转,28例(24.13%)持续原状,19例(16.39%)由于失访或其他原因转归情况不详。在所有患者治疗过程中,1例(0.05%)患者发生2级间质性肺炎,未发生患者因不良反应导致的死亡。结论恩沙替尼在真实世界人群中应用具有较好的安全性,主要不良反应表现为皮疹,多为轻度,≥3级不良反应发生率较低,不良反应整体耐受、可控。

Objective To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC)in the real-world clinical setting.Methods Clinical data of 2221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment(225 mg/d)from December 16,2020 to December 16,2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients(≥65 years old).Results Among the total 2221 patients,511 patients(23.01%)experienced adverse events,including 8 patients(0.36%)who experienced serious adverse events.Adverse events led to dose modification in 67 patients(3.02%)and discontinuation in 18 patients(0.81%).The common adverse events were rash(407/2221,18.33%),pruritus(41/2221,1.85%),constipation(41/2221,1.85%),and facial edema(31/2221,1.40%).Thirty-six patients(1.62%)experienced≥grade 3 adverse events.After symptomatic treatment of 511 patients with adverse reactions,50 patients(9.78%)were healed,271 patients(53.03%)were improved,120 patients(23.48%)were persisted,and 70 patients(13.71%)were unknown due to loss of follow-up or other reasons.Forty-three patients(1.94%)reported 57 unintended adverse reactions.Among the 599 elderly patients,116 patients(19.37%)experienced adverse events,including 1 patient(0.17%)who experienced serious adverse events.Adverse events led to dose modification in 25 patients(4.17%)and discontinuation in 5 patients(0.83%).The common adverse events of elderly patients were rash(88/599,14.69%),constipation(14/599,2.34%),facial edema(12/599,2.00%),and pruritus(10/599,1.67%).Twelve patients(2.00%)experienced≥grade 3 adverse events.Among the 116 elderly patients with adverse reactions following the symptomatic treatment,11 patients(9.48%)were healed,58 patients(50.00%)were improved,28 patients(24.13%)were persisted,and 19 patients(16.39%)were unknown due to loss of follow-up or other reasons.During the treatment,1 patient(0.05%)experienced grade 2 interstitial lung disease,and no patient died due to adverse events.Conclusion Ensartinib has a favorable safety profile in the real-world populations,with the most frequent adverse events being rash,mostly mild,and low incidence of≥grade 3 adverse events.Overall,adverse reactions were tolerable and manageable.