Abstract：
BACKGROUND: Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify real-world evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS).
METHODS: We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib.
RESULTS: Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I2 > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate).
CONCLUSIONS: The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting.
METHODS: We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib.
RESULTS: Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I2 > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate).
CONCLUSIONS: The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting.
摘要：
背景：2016年，克唑替尼被批准用于治疗ROS原癌基因1（ROS1）基因融合的晚期非小细胞肺癌（aNSCLC）患者。我们进行了系统的文献综述，以确定真实世界证据（RWE）研究，并使用客观缓解率（ORR）的荟萃分析（MA）评估克唑替尼的疗效和安全性。真实世界无进展生存期（PFS），总生存率（OS）。
方法：我们搜索了MEDLINE®，Embase,2016年1月至2023年3月，CochraneCENTRAL使用Ovid®进行已发表的单臂或比较RWE研究，评估接受克唑替尼单药治疗ROS1基因融合aNSCLC的患者(N≥20)。使用R中的metafor软件包得出ORR和3/4级不良事件（AE）的汇总估计值，而使用已发表的Kaplan-Meier曲线中的重建个体患者数据得出真实PFS（rwPFS）和OS的汇总估计值。主要分析包括所有研究，而与克唑替尼治疗方案无关；使用评估接受一线克唑替尼的患者的研究进行亚组分析（SA）。
结果：14项研究符合资格标准，被认为对MA是可行的。对于主要分析，合并的ORR(N=9项研究)为70.6%(95%置信区间[CI]：57.0，81.3)，中位rwPFS为14.5个月(N=11项研究)，OS为40.2个月（N=9项研究）。在SA中,合并ORR(N=4项研究)为81.1%(95%CI:76.1,85.2),rwPFS(N=4项研究)和OS(N=2项研究)中位数为18.1个月和60个月,分别。所有MAs均具有显著异质性(I2>25%)。18.7%的患者发生3/4级AE（汇总估计）。
结论：本研究的结果与临床试验数据一致，集体来看，支持克唑替尼在真实世界中作为ROS1aNSCLC患者的不同治疗方法安全有效.
方法：我们搜索了MEDLINE®，Embase,2016年1月至2023年3月，CochraneCENTRAL使用Ovid®进行已发表的单臂或比较RWE研究，评估接受克唑替尼单药治疗ROS1基因融合aNSCLC的患者(N≥20)。使用R中的metafor软件包得出ORR和3/4级不良事件（AE）的汇总估计值，而使用已发表的Kaplan-Meier曲线中的重建个体患者数据得出真实PFS（rwPFS）和OS的汇总估计值。主要分析包括所有研究，而与克唑替尼治疗方案无关；使用评估接受一线克唑替尼的患者的研究进行亚组分析（SA）。
结果：14项研究符合资格标准，被认为对MA是可行的。对于主要分析，合并的ORR(N=9项研究)为70.6%(95%置信区间[CI]：57.0，81.3)，中位rwPFS为14.5个月(N=11项研究)，OS为40.2个月（N=9项研究）。在SA中,合并ORR(N=4项研究)为81.1%(95%CI:76.1,85.2),rwPFS(N=4项研究)和OS(N=2项研究)中位数为18.1个月和60个月,分别。所有MAs均具有显著异质性(I2>25%)。18.7%的患者发生3/4级AE（汇总估计）。
结论：本研究的结果与临床试验数据一致，集体来看，支持克唑替尼在真实世界中作为ROS1aNSCLC患者的不同治疗方法安全有效.
