ArticleTranslational oncology2024
Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors.
Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 6 citations in OpenAlex.
- A nomogram prediction model for brain metastases in patients with lung adenocarcinoma.Oncology letters · 2026Article
- Structure-based classification for differential tyrosine kinase inhibitors efficacy of EGFR exon 19 deletions in non-small cell lung cancer.Science China. Life sciences · 2026Article
- Article
- Salvage dacomitinib plus intraventricular pemetrexed for leptomeningeal metastasis after failure of third‑generation EGFR‑TKIs in EGFR‑mutant NSCLC: an ambispective cohort study.Journal of neuro-oncology · 2026Article
- The characteristics and prognoses of 72 postoperative synchronous multiple primary lung cancer patients.World journal of surgical oncology · 2025Article
- Potential supplementary tumor markers for liquid biopsy in non-small cell lung cancer.Experimental biology and medicine (Maywood, N.J.) · 2025Article
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12 authors at 5 institutions in 1 country.
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Abstract
backgroundThis study compared the clinical efficacy of first-, second-, and third-generation tyrosine kinase inhibitors (TKIs) in previously untreated non-small cell lung cancer (NSCLC) patients harboring uncommon epidermal growth factor receptor (EGFR) exon 19delins variants.
methodsWe retrospectively analyzed the clinical outcomes of NSCLC patients with EGFR exon 19delins mutations who were treated with third- and first-generation EGFR TKIs. In vitro and in vivo studies were conducted to verify the sensitivity of these mutations to distinct generations of TKIs. Molecular simulation was used to investigate the structural characteristics of the EGFR mutant molecules.
resultsIn a multicenter cohort of 1,526 patients, 37 (2.4 %) had uncommon EGFR 19delins mutations. Twenty-four patients were treated with first-generation EGFR TKIs, and third-generation TKIs were administered to ten patients as frontline therapy. Patients carrying EGFR exon 19delins mutations who were given third-generation TKIs exhibited comparatively shorter progression-free survival (PFS) and overall survival (OS) in relation to those who received first-generation EGFR inhibitors; median PFS: 6.9 months vs. 19.1 months (p < 0.001), Median OS: 19.1 months vs. 32.6 months (p < 0.001). In vivo and in vitro studies revealed that uncommon EGFR 19delins variants exhibit limited sensitivity to third-generation EGFR inhibitors in contrast to first- and second-generation EGFR inhibitors. The molecular binding affinity of third-generation EGFR TKIs toward uncommon EGFR 19delins mutations was less than that of first- and second-generation EGFR inhibitors.
conclusionsUncommon EGFR 19delins variants respond poorly to third-generation EGFR inhibitors in NSCLC. Uncommon EGFR 19delins mutations may serve as an unfavorable predictive factor for the efficacy of third-generation EGFR TKI therapy, offering potential guidance for future clinical decision-making.
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