Fatal Interstitial lung disease induced by Osimertinib: a case report

ABSTRACT

Introduction: Osimertinib is a selective third-generation EGFR-TKI inhibitor with an inhibitory effect on the T790M mutation. Interstitial lung disease (ILD) occurred in 3.9% of the Osimertinib-treated patients (with 0.4% fatal cases). Methods: Case report of fatal ILD induced by Osimertinib in a patient with metastatic lung adenocarcinoma. Results: We present the case of an 81-year-old female patient diagnosed with stage IVB lung adenocarcinoma (May 2020) with pulmonary, adrenal, and brain metastasis. Genetic sequencing showed an exon 19 deletion. She started erlotinib until documentation of disease progression in January 2021. In this context, she performed a liquid biopsy with the detection of a T790M resistance mutation. She started Osimertinib in February 2021. Her past medical history showed diabetes and dyslipidemia. Two months after starting Osimertinib, she went to the emergency department (ER) with a one-week evolution with progressive dyspnea, cough, and fever. Upon admission to the ER, she was conscious and cooperative, with respiratory distress signs, normal blood pressure, and hypoxemia. She had decreased breath sounds, and coarse crackles were audible bilaterally. In the blood sampling, Haemoglobin was 7.7 mmol/L, creatinine 0.08 mmol/L, platelets 257000x10ˆ9/L, C-reactive protein 28.6 nmol/L, and NT-proBNP 98 pmol/L. Rt-PCR for sars-CoV-2 detection was negative. X-ray showed bilateral diffuse infiltrates. She started oxygen therapy via nasal cannula at 3l/min and IV antibiotics. ABG values were pH 7.44, pCO2 37 mmHg, pO2 69 mmHg, HCO3 26 mEq/L, sO2 94%. On reassessment after 3 hours, she presented worsening dyspnea and dizziness, with higher oxygen needs (venturi mask, 60%). Chest CT angiography showed extensive bilateral diffuse ground-glass densification with crazy-paving areas. It also showed no signs of pulmonary embolism. We admitted her to a level 2 ICU unit for surveillance. Due to suspected drug toxicity, she started Methylprednisolone pulses (1000mg/3days). Six hours after admission, due to hypoxemia worsening, non-invasive ventilation was started with the need to escalate oxygen therapy to 100% FiO2. At 24h, she showed clinical and blood analysis improvement. Nonetheless, she still needed 100% fiO2 to maintain >92% oxygen saturation. On the 4th day of hospitalization, she was hypotensive, prostrated, and with little reaction to painful stimulation. She started palliative treatment and died on the same day. Conclusions: ILD is a rare adverse effect of the treatment with Osimertinib, and fatal ILD is even rarer. The time from starting Osimertinib to this side effect is variable between patients. Awareness is necessary for a rapid diagnosis and early treatment. [Formula presented] Keywords Osimertinib, Intersticial Lung Disease, Adverse effect