克唑替尼战胜了晚期ALK阳性NSCLC：3期和4期临床试验的Meta分析

Crizotinib Wins the Battle against Advanced ALK-Positive NSCLC: A Meta Analysis for Phase 3 and 4 Clinical Trails

摘要: 目的：ALK阳性的非小细胞肺癌约占所有非小细胞肺癌的2%~7%。第一代ALK-TKIs药物克唑替尼已广泛应用于临床治疗。本Meta分析采用随机效应模型，目的是总结克唑替尼3、4期临床试验的效果，评价克唑替尼与化疗相比的疗效和安全性。方法：我们使用无进展生存(progression-free survival, PFS)、客观有效率(objective response rate, ORR)、3/4级药物不良反应(adverse drug event, ADE)的发生率和临床结果，包括：完全缓解(complete response, CR)、部分缓解(partial response, PR)、稳定病(SD, stable disease)和进展病(progressive disease, PD)来评估克唑替尼的疗效和安全性。结果：本Meta分析共纳入7项研究(1121例患者)。本Meta分析结果如下：克唑替尼组患者的PFS明显长于化疗组。HR值和95% CI为0.45 (0.38~0.53)；克唑替尼组患者的ORR明显高于化疗组。OR值和95% CI为0.18 (0.13~0.24)。3/4级ADE无显著性差异。OR值和95% CI为0.91 (0.68~1.21)。患者受益于克唑替尼，CR发生率明显升高，PD发生率明显降低。结论：本Meta分析证实了克唑替尼的有效性和安全性。克唑替尼治疗ALK阳性NSCLC明显优于化疗。本标准还将用于评估下一代ALK-TKIs的临床疗效。

Abstract: Purpose: ALK positive non-small cell lung cancer (NSCLC) accounts for about 2%~7% of all NSCLC. The first generation of ALK-TKIs drug, crizotinib, has been widely used in clinical treatment. The purpose of this Meta analysis using the random effect model is to summarize the effect of phase 3/4 clinical trials of crizotinib and to evaluate the efficacy and safety of crizotinib compared with chemotherapy. Methods: We use the progression free survival (PFS), objective response rate (ORR), the incidence of grade 3/4 adverse drug effect (ADE) and clinical outcomes including: complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) to evaluate the efficacy and safety of crizotinib. Results: A total of 7 studies (1121 patients) were included in this Meta analysis. The results of this Meta analysis are as follows: the PFS of patients in crizotinib group was significantly longer than chemotherapy group. The HR value and 95% CI were 0.45 (0.38~0.53); the ORR of patients in crizotinib group was significantly higher than chemotherapy group. The OR value and 95% CI were 0.18 (0.13~0.24). Meanwhile, there was no significant difference in grade 3/4 ADE. The OR value and 95% CI were 0.91 (0.68~1.21). Patients benefited from crizotinib; the incidence of CR was significantly increased while the incidence of PD sig-nificantly reduced. Conclusions: This Meta analysis confirms the efficacy and safety of crizotinib. Crizotinib is obviously superior to chemotherapy in the treatment of ALK positive NSCLC. The standard is also established for the evaluation of the clinical efficacy of the next generation of ALK-tyrosine kinase inhibitors (TKIs).