Systematic Literature Review (SLR) and Meta-Analysis of Crizotinib Versus Conventional Chemotherapy in First-Line Treatment for ROS-1 Rearranged Non-Small Cell Lung Cancer

OBJECTIVES: Lung cancer is a main cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the major histologic subtype and accounts for 80% of all lung cancers. Approximately 1%-2% of patients with NSCLC harbor ROS-1 rearrangement, which has now become a successful target of multiple tyrosine kinase inhibitors (TKIs). The aim of our SLR/meta-analysis was to assess the impact of newer therapies such as crizotinib in comparison to traditional chemotherapies in real world setting.

METHODS: An SLR was conducted to identify observational studies that evaluated progression-free survival (PFS) and overall response rate (ORR) in patients with unresectable locally advanced, advanced/metastatic ROS1 NSCLC cancer in first line setting from database inception to May 2023. Key biomedical databases such as Embase and Medline were searched supplemented by internet handsearching. Screening and data extractions were performed by two independent reviewers with any conflicts resolved by a third reviewer. Meta-analysis was performed using the Metaprop package in R-4.1.3 software. The effect size for Hazard Ratio (HR) and ORR were all pooled with 95% confidence intervals (CIs). Heterogeneity was considered significant for I₂ - statistic greater than or equal to 50% or the p value was ≥ 0.10, and then the random-effects model was adopted.

RESULTS: Our meta-analysis of observational studies revealed a pooled PFS HR of 0.34 (95% CI: 0.27-0.43) for crizotinib compared to conventional chemotherapy. Crizotinib demonstrated a significantly higher ORR of 85% (95% CI: 80%-89%) compared to 42% (95% CI: 30%-35%) observed with conventional chemotherapy. The relative difference in ORR between the TKI and conventional chemotherapy was notable at 41% (95% CI: 29%-63%).

CONCLUSIONS: The research shows that crizotinib continues to demonstrate a favorable treatment response compared to chemotherapies for patients with unresectable locally advanced, advanced/metastatic ROS1 NSCLC cancer in real world setting.