阿来替尼治疗晚期EML4-ALK融合基因阳性非小细胞肺癌110例

Alectinib in treatment of 110 patients with advanced EML4-ALK fusion gene positive non-small cell lung cancer

目的观察阿来替尼治疗晚期棘皮动物微管相关蛋白4间变性淋巴瘤激酶(EML4-ALK)融合基因阳性非小细胞肺癌(NSCLC)的疗效及安全性。方法回顾性分析晚期EML4-ALK融合基因阳性NSCLC患者110例,接受阿来替尼600 mg po bid治疗,用药直至疾病进展或不能耐受的不良反应为止。观察治疗3个月后的疗效,采用卡方检验及logistics回归法进行单因素和多因素分析,评估多个临床因素与阿来替尼疗效的关系;并记录不良反应发生情况。结果所有患者客观缓解率(ORR)为73.6%,疾病控制率(DCR)为100.0%。体力状况(PS)评分0~1分者ORR显著高于PS评分2分及以上者(P<0.05),使用阿来替尼一线治疗者ORR较二线及以上治疗者显著升高(P<0.05),克唑替尼耐药患者ORR较未使用过克唑替尼者显著降低(P<0.05)。进一步多因素回归分析发现,PS评分(OR=0.28,95%CI:0.07~1.05,P=0.059)、阿来替尼治疗线数(OR=0.56,95%CI:0.09~3.45,P=0.529)及是否克唑替尼耐药(OR=0.46,95%CI:0.08~2.50,P=0.367)均不是ORR的独立影响因素。截至2020年9月30日,中位无进展生存期(mPFS)未达到。阿来替尼治疗总不良反应发生率为78.2%,其中Ⅲ~Ⅳ级不良反应包括胆红素升高和贫血各1例;未发生治疗相关死亡事件。结论阿来替尼治疗晚期EML4-ALK融合基因阳性NSCLC患者有较好的疗效,且不良反应可以耐受。

AIM To observe the efficacy and safety of alectinib in the treatment of advanced echinoderm microtubule associated protein like 4 anaplastic lymphoma kinase(EML4-ALK) fusion gene positive non-small cell lung cancer(NSCLC). METHODS A retrospective analysis was conducted of 110 patients with advanced EML4-ALK fusion gene positive NSCLC who were treated with alectinib 600 mg po bid until the disease progression or intolerable adverse reactions.The efficacy of treatment after 3 months was observed. The univariate and multivariate analysis were performed by chisquare test and logistics regression to evaluate the relationship between multiple clinical factors and the efficacy of alectinib,and the occurrence of adverse reactions were recorded. RESULTS The objective response rate(ORR) and disease control rate(DCR) of all patients were 73.6% and 100.0%, respectively. The ORR of patients with peoformance status(PS) score of 0-1 were significantly higher than those of patients with PS score of 2 or above(P < 0.05). The ORR of the firstline treatment of alectinib was significantly higher than those of the second-line and above treatment(P < 0.05). And the ORR of crizotinib-resistant patients were significantly lower than those of the untreated patients(P < 0.05). The multivariate regression analysis showed that PS score(OR = 0.28,95%CI: 0.07 to 1.05,P = 0.059), the number of treatment lines of alectinib(OR = 0.56,95%CI: 0.09 to 3.45,P = 0.529) and whether resistant to crizotinib or not(OR = 0.46,95%CI: 0.08 to 2.50,P = 0.367) were not independent factors of ORR. By the time of September 30, 2020, the median progressionfree survival(mPFS) has not been achieved. The total incidence of adverse events was 78.2%, including 1 case of bilirubin elevation and 1 case of anemia in grade Ⅲ-Ⅳ. No treatment-related death occurred. CONCLUSION Alectinib is effective in the treatment of advanced EML4-ALK fusion gene positive NSCLC, and the adverse reactions are well tolerated.