Case Report: A successful rechallenge with aumolertinib after osimertinib-induced severe interstitial lung disease

Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), demonstrates significant efficacy in treating non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, EGFR-TKI-induced interstitial lung disease (ILD) is a recognized and severe adverse reaction that can be fatal. Given the often limited patient acceptance of chemotherapy, there is currently no international consensus on the efficacy and safety of rechallenging with an EGFR-TKI following EGFR-TKI-induced ILD. Case Summary: We report the case of a 73-year-old male with stage IV lung adenocarcinoma carrying an EGFR exon 19 deletions (Ex19del) mutation, who received first-line osimertinib at 80 mg daily. In the third month of treatment, the patient developed grade IV (CTCAE v5.0) ILD, presenting with dyspnea, chest tightness, dry cough, and fever. Arterial blood gas analysis indicated type I respiratory failure, and a chest CT scan revealed new bilateral patchy and reticular opacities. As high-flow nasal cannula oxygen failed to maintain adequate oxygen saturation, the patient was transferred to the intensive care unit (ICU), where he received endotracheal intubation, anti-inflammatory therapy with methylprednisolone, and anti-infective treatment. After 18 days, he recovered well and was discharged. Post-discharge, oral corticosteroid therapy was continued, and nintedanib was administered for its anti-fibrotic effects. The patient subsequently declined chemotherapy. Two months after corticosteroid therapy, EGFR-TKI treatment was rechallenged with aumolertinib at a reduced dose of 55 mg daily. After 1 month of treatment, the patient experienced no recurrence of dyspnea or other respiratory symptoms. A follow-up CT scan indicated resolution of the interstitial pneumonia and shrinkage of the pulmonary tumor. The aumolertinib dose was then increased to the standard 110 mg daily and treatment was continued. Conclusion: Rechallenging with an EGFR-TKI after osimertinib-induced ILD remains highly challenging, particularly for grade 3 or higher ILD. In this case, following an adequate course of corticosteroid and anti-fibrotic therapy, successful rechallenge was achieved by initiating treatment with a low dose of aumolertinib, which was later escalated to the conventional dose.