Abstract
Non-small cell lung cancer (NSCLC) remains a major contributor to cancer-related deaths globally. Advances in tumor molecular profiling have led to the identification of actionable oncogenic alterations, including rearrangements involving the anaplastic lymphoma kinase (ALK) gene, which occur in a distinct subset of NSCLC patients. Crizotinib, an early-generation ALK-targeted tyrosine kinase inhibitor, has been widely used in this population; however, its overall clinical benefit relative to conventional chemotherapy continues to warrant systematic evaluation. This study synthesized published clinical evidence to assess objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) among patients with ALK-positive NSCLC treated with crizotinib. A meta-analysis incorporating 38 eligible studies retrieved from PubMed was conducted, with inclusion criteria based on comparable study design and outcome reporting. Statistical analyses were performed using Review Manager 5 (The Cochrane Collaboration, London, England, UK), and sensitivity analyses were undertaken following exclusion of studies deemed to have a high risk of bias. Survival outcomes were summarized using reported means and ranges across multiple follow-up intervals, and treatment effects were quantified using odds ratios (ORs) with corresponding p-values. Compared with chemotherapy, crizotinib treatment resulted in a markedly higher ORR (OR = 6.86; 95% CI, 4.39-10.73; p < 0.00001). Reported median PFS ranged from 6.8 to 19 months in the crizotinib cohorts, versus 2.4 to seven months among chemotherapy-treated patients. At six and 12 months, PFS rates for crizotinib-treated patients ranged from 53.13% to 85.32% and from 14.29% to 61.7%, respectively. Pooled analyses demonstrated significant improvements in both six-month and 12-month PFS relative to chemotherapy (OR = 2.84; 95% CI, 2.23-3.61; p < 0.00001 and OR = 4.33; 95% CI, 2.64-7.10; p < 0.00001, respectively). In contrast, although one- and two-year OS rates for crizotinib ranged from 27.5% to 97.1% and from 48.3% to 87.5%, no statistically significant differences in OS were observed when compared with chemotherapy at either time point (one-year OS: OR = 1.56; 95% CI, 0.81-2.99; p = 0.18; two-year OS: OR = 1.84; 95% CI, 0.95-3.58; p = 0.07). Overall, these findings indicate that while crizotinib confers substantial improvements in tumor response and disease control, its effect on long-term survival outcomes appears limited. Given the multifactorial determinants of OS, future investigations incorporating more granular patient stratification may be necessary to better delineate the role of crizotinib within the evolving treatment landscape for ALK-positive NSCLC.