Crizotinib 250mg capsules

PurposeTo assess the possible effect of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) on the health-related quality of life (HRQoL) in patients with ALK-positive non-small cell lung cancer (NSCLC).MethodsA systematic search was performed in PubMed, Web of Science, Embase, and ClinicalTrials.gov to identify literature published between January 2010 and January 2025. Publications reported quantitative assessments of HRQoL in ALK-positive NSCLC patients treated with ALK-TKIs were included. Meta-analyses were performed using random effect models.ResultsA total of 805 records were identified, of which 21 were analyzed in the meta-analysis. Compared to crizotinib, next-generation ALK-TKIs showed statistically significant delayed time to deterioration (TTD) in global health status measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.67 to 0.96). Brigatinib and alectinib demonstrated superior TTD in fatigue symptom score of EORTC QLQ-C30 compared to crizotinib (HR: 0.71; 95% CI: 0.54 to 0.92). Regarding between-arm comparisons from baseline, brigatinib and lorlatinib outperformed crizotinib in global health status, physical and emotional functioning, and symptoms scores of nausea and vomiting, fatigue, constipation, and appetite loss using EORTC QLQ-C30.ConclusionsThis study is by far the most comprehensive systematic review and meta-analysis on HRQoL among ALK-positive NSCLC patients treated with ALK-TKIs. These findings extended prior literature by conducting a granular comparison of all available ALK-TKIs across multiple endpoints and highlighted the improved performance of next-generation ALK-TKIs in enhancing HRQoL for ALK-positive NSCLC patients.

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OBJECTIVES: To identify optimal treatments and sequencing strategies that maximize efficacy, safety, and net health benefits (NHB, a comprehensive measure of safety and efficacy) for ALK-positive non-small-cell lung-cancer (NSCLC). METHODS: Related data from phase Ⅱ-Ш clinical trials targeting ALK-positive NSCLC was identified through a systematic search of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov. Progression-free survival (PFS) and overall survival (OS) estimates were derived from Kaplan-Meier curves using individual participant data. Life-year gained (LYG) was the main efficacy outcome. Safety was evaluated by all-cause grade 3 + adverse events. Survival outcomes across treatment sequences were projected using a clock-reset semi-Markov model. Quality-adjusted life year (QALY) was used as the metric for NHB to evaluate the comprehensive value of treatment effectiveness and safety. Sensitivity and scenario analyses were conducted to validate our findings. RESULTS: A total of 27 studies were included. Lorlatinib maximized LYG and NHB as both first-line and post-crizotinib second-line therapy. Alectinib led LYG and NHB after chemotherapy resistance, while brigatinib topped after alectinib resistance. Chemotherapy followed by alectinib or brigatinib, resulted in the highest LYG for first-line to second-line PFS, with the alectinib-brigatinib sequence delivering the highest NHB. For first-line to third-line PFS, the chemotherapy-alectinib-brigatinib sequence maximized survival, while alectinib-brigatinib-lorlatinib was optimal for NHB. Frontline second-generation ALK-TKI enhanced boost survival and NHB, using first-generation ALK-TKI before chemotherapy had little impact on survival but improved initial NHB. Safety profiles emphasized alectinib as the safest first-line option, with iruplinalkib being the most favorable option after crizotinib resistance. Uncertainty analysis indicated that the findings were robust. CONCLUSIONS: According to current analyses, lorlatinib is an optimal first-line therapy. Alectinib and brigatinib are effective subsequent treatments in cases of non-lorlatinib resistance. First-line ALK-TKIs optimize patient benefits, and carefully sequenced treatments offer substantial survival and NHB across all stages of therapy.

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BackgroundAnaplastic lymphoma kinase (ALK) fusion is an important therapeutic targets in non-small cell lung cancer (NSCLC). Different ALK variants may affect the efficacy of targeted therapies. This meta-analysis systematically assesses the impact of different ALK variants on the clinical outcomes of ALK TKI treatment.MethodsBy systematically searching PubMed, Embase, and Web of Science databases, we collected relevant studies published from January 1,1994 to September 30, 2025. The relationship between different ALK variations and treatment efficacy was evaluated by combining hazard ratio (HR) and 95% confidence interval (CI). The quality of studies was evaluated using tools such as the Newcastle-Ottawa Scale (NOS) and the Cochrane risk-of-bias tool.ResultsA total of 30 studies involving 2737 patients with ALK-positive NSCLC were included. Comparison between EML4-ALK variant 1 (V1) and variant 3 (V3) showed that V3 was associated with shorter progression-free survival (PFS) in patients receiving ALK TKI treatment (HR = 1.53, 95%CI:1.17-1.99, p=0.002). Subgroup analysis showed that the adverse effect of V3 was more pronounced in patients treated with crizotinib (HR = 1.40, 95%CI: 1.00-1.96, p=0.049), in the first line treatment setting (HR = 1.83, 95%CI: 1.34-2.50, pConclusionEML4-ALK v3 may be an important negative prognostic factor for the efficacy of targeted therapy in ALK positive NSCLC. Subgroup analysis indicated that the poor prognosis associated with v3 was particularly evident in patients treated with crizotinib, in the first line setting, and in those assessed by NGS. However, due to limited data on newer generation ALK TKIs and the presence of heterogeneity in some of the comparison groups, definitive conclusions cannot be drawn. Prospective studies with standardized molecular subtyping are still needed before considering clinical stratification based on ALK variant types.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251229641, identifier CRD420251229641.

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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.

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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed in a subset of patients with non-small cell lung cancer (NSCLC). Since the approval of crizotinib, which was the first ALK tyrosine kinase inhibitor (TKI), the treatment landscape has rapidly evolved with the development of multiple next-generation TKIs and investigational agents. A structured review of clinical trials registered on ClinicalTrials.gov was conducted to identify studies evaluating therapies in ALK-positive NSCLC, including phase I-IV trials in adult populations, regardless of recruitment status. Trials were screened for ALK-specific relevance and key outcomes including progression-free survival (PFS) and objective response rate (ORR) were extracted. Central nervous system (CNS) activity and resistance mutation profiles were collected from published literature when available. A meta-analysis of ORR was conducted on a subset of 41 trials comprising 66 evaluable cohorts with sufficient efficacy data. Studies evaluated first- through third-generation ALK TKIs, combination regimens, and experimental agents. Meta-analysis of 6,382 patients showed a pooled ORR of 58.5% [95% confidence interval=57.3-59.7], with higher response rates in treatment-naive versus pretreated cohorts (71.8% vs 48.4%). Weighted median PFS was 13.8 months in treatment-naive and 9.8 months in pretreated cohorts. CNS activity, summarized from published reports, indicated superior intracranial efficacy of later generation TKIs. ALK-targeted therapies have significantly improved outcomes in ALK-positive NSCLC. However, CNS progression, acquired resistance, and optimal treatment sequencing continue to limit outcomes. This review synthesizes current evidence to guide clinical practice and future investigations.

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