ArticleThoracic cancer2025
Impact of EML4-ALK Variants and TP53 Status on the Efficacy of ALK Inhibitors in Patients With Non-small Cell Lung Cancer.
Article in Thoracic cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A meta-analysis of the impact of different ALK variants on targeted therapy efficacy in advanced non-small cell lung cancer.Frontiers in oncology · 2026Pooled it
- Retrospective study of alectinib treatment among variants ofTranslational lung cancer research · 2026Article
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9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe clinical implications of different EML4-ALK fusion variants remain poorly elucidated in the era of second-generation ALK inhibitors.
methodsThis was a retrospective cohort study, wherein patients diagnosed with locally advanced or metastatic non-small cell lung cancer harboring EML4-ALK fusion were stratified into two cohorts based on their first-line treatment: Cohort 1 received alectinib, while Cohort 2 received crizotinib. Statistical analysis was employed to investigate the impact of different EML4-ALK variants and TP53 status on the efficacy of first-line ALK-TKIs.
resultsFinally, 49 patients were enrolled in cohort 1 and 53 patients in cohort 2. In cohort 1, patients with long EML4-ALK fusion variants exhibited prolonged PFS (NR vs. 34.0 m, p = 0.004, HR = 0.30, 95% CI: 0.12-0.74) and an elevated 5-year OS rate (93.3% vs. 68.4%, p = 0.020, HR = 0.12, 95% CI: 0.02-0.62) compared to those with short variants. The median PFS was not reached in TP53-wt group and 47.0 m in TP53-mut group (p = 0.087, HR = 0.44, 95% CI: 0.17-1.17). The TP53-wt group exhibited a superior 5-year OS rate (100% vs. 77.8%, p = 0.030) compared to TP53-mut group. In cohort 2, the median PFS was 14.0 m in long variant group and 12.9 m in short variant group (p = 0.094, HR = 0.65, 95% CI: 0.37-1.13); the median OS was not reached in long variant group and 69.2 m in short variant group (p = 0.254, HR:0.62, 95% CI: 0.27-1.42). However, the efficacy of first-line crizotinib did not appear to be influenced by the TP53 status.
conclusionsEML4-ALK short variants and TP53 mutations are both adverse factors for first-line alectinib efficacy, but they have little effect on first-line crizotinib.
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