Successful treatment with osimertinib and its subsequent resistance mechanism in a patient with non-small-cell lung cancer harboring acquired EGFR T790M mutation after recovery from AC0010-induced interstitial lung disease

OBJECTIVE: Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)can occasionally lead to interstitial lung disease (ILD), and the appropriate treatment after recovery from ILD remains controversial. AC0010 is an investigational third-generation TKI used in China to selectively target the T790M mutation. Here, we describe a patient who developed ILD after AC0010 treatment and was then successfully re-challenged with osimertinib. METHODS: The patient was a 67-year-old male with a diagnosis of metastatic pulmonary adenocarcinoma with an L858R mutation on exon 21. Acquired T790M mutation was confirmed by re-biopsy after progression on erlotinib treatment. The patient was treated with AC0010, and developed ILD 54 days after treatment initiation. Following his recovery from ILD, osimertinib (80 mg/day) was administered with no adverse effects. After progression on osimertini\b 11 months later, a histological transformation from adenocarcinoma to large-cell neuroendocrine carcinoma was confirmed by re-biopsy, with a marked increase in serum neuron-specific enolase. CONCLUSIONS: This is the first report of interstitial pneumonitis caused by AC0010. Osimertinib re-challenge after recovery from ILD was a safe and effective treatment option. Our report further highlights that pathological transformation of large-cell neuroendocrine carcinoma represents one of the resistance mechanisms of osimertinib, and may be accompanied by an increase in serum neuron-specific enolase.