ArticleTranslational lung cancer research2026
Dacomitinib for EGFR-L858R-mutated non-small cell lung cancer following acquired resistance to third-generation EGFR-TKIs: a retrospective real-world study.
Article in Translational lung cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Management of non-small cell lung cancer (NSCLC) after acquired resistance to third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an unmet clinical need with no consensus on optimal strategies. Encouraging efficacy of subsequent dacomitinib treatment was observed in clinical practice, yet unproven. Therefore, this study aimed to evaluate the efficacy and safety of dacomitinib in patients with advanced EGFR-L858R-mutated NSCLC after acquired resistance to third-generation EGFR-TKIs, with exploratory assessment of intracranial activity in patients with brain metastases. Methods: A retrospective real-world study enrolled consecutive advanced EGFR-L858R-mutated NSCLC patients with third-generation EGFR-TKI resistance from Shandong Cancer Hospital and Institute (November 2020-March 2024). All received dacomitinib. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Results: Forty-two patients were included, with a median follow-up of 16.3 months (3.0-35.0 months) and 4 median treatment lines. ORR and DCR were 33.3% and 78.6%, respectively. Median PFS was 5.7 months [95% confidence interval (CI): 4.4-6.9], and median OS was 26.5 months (95% CI: 15.2-37.8). Exploratory analysis showed no significant differences in median PFS (5.4 Conclusions: Dacomitinib is a promising, well-tolerated option for EGFR 21-L858R-mutated NSCLC patients with third-generation EGFR-TKI resistance, warranting prospective clinical trials for validation.
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