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Life sciences · Journal article
Medicine · November 6, 2026
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Rationale: First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective in EGFR-mutant non-small cell lung cancer (NSCLC); however, drug-induced interstitial lung disease (ILD) remains a rare but potentially fatal adverse event. The safety and efficacy of EGFR-TKI rechallenge – either with the same agent or an alternative one – following ILD resolution are not established and represent a significant clinical knowledge gap. Patient concerns: A 53-year-old never-smoking woman with stage IV lung adenocarcinoma – detected to harbor an L858R mutation in exon 21 of the EGFR gene – developed progressive dyspnea and hypoxemia after 2 months of first-line gefitinib therapy, despite confirmed initial radiographic and clinical response. Diagnoses: The patient was diagnosed with grade 3 gefitinib-associated ILD. Interventions: With the discontinuation of gefitinib, the patient was given methylprednisolone to resolve ILD. To control advanced lung adenocarcinoma progression, the patient was subjected to 6 cycles of treatment using pemetrexed, carboplatin, and bevacizumab, with measurable tumor shrinkage, followed by maintenance therapy with bevacizumab. Furthermore, given the tumor progression 14 months later, the patient was prescribed docetaxel plus bevacizumab to restore control. Ten months later, the patient experienced disease progression and strongly requested to use EGFR-TKIs again given prior response to EGFR-TKI. The patient was rechallenged with almonertinib, a third-generation EGFR-TKI, and methylprednisolone. Outcomes: The patient had measurable tumor shrinkage, with sustained tumor control and no recurrence of pulmonary toxicity. As of last follow-up, she maintained progression-free survival for approximately 8 months on almonertinib. Lessons: This case provides a hypothesis-generating observation, illustrating feasibility only in highly‑selected patients with EGFR‑mutant NSCLC and prior severe TKI‑related ILD. With prophylactic corticosteroids and rigorous surveillance, third‑generation EGFR‑TKI may represent a tentative clinical option for such patients, but general safety cannot be inferred from this single case.