Successful Rechallenge with Osimertinib after Very Acute Ons
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A 71-year-old non-Hispanic white female, never-smoker was incidentally diagnosed with advanced-stage non-small-cell lung cancer after presenting with acute right-sided shoulder pain secondary to a pathological fracture of the humerus from a metastatic lytic lesion. Diagnostic computed tomography (CT) images demonstrated right lower lobe lung mass, with widespread lymphadenopathy and multiple lytic lesions. Diagnostic biopsy of the humeral lesion revealed a lung adenocarcinoma and the immune-histochemistry was positive for CK-7, TTF-1, Napsin A, and PAX-8. Molecular testing revealed 0% PDL-1 expression, mutation testing negative for ALK and ROS1 but positive for EGFR exon 19 deletion (E19del) driver mutation. She was diagnosed with Stage IV lung cancer (cT3, cN2, and pM1) and started on osimertinib 80 mg tablet once a day as a first-line agent based on molecular tumor profiling.

After 1 week of therapy, she developed rapidly progressive shortness of breath and was hospitalized for acute hypoxic respiratory failure. On physical examination, her vital signs were remarkable for tachypnea, tachycardia, and decreased breath sounds bilaterally. Differential diagnoses included community-acquired pneumonia, COVID-19 pneumonia, cardiogenic pulmonary edema, acute pulmonary embolism, progressive disease, lymphangitic carcinomatosis, and drug-induced pneumonitis as a diagnosis of exclusion. Laboratory workup revealed mild leukocytosis (WBC-12,500/µL) with left shift, lactate of 2.5 mmol/L, C-reactive protein (CRP) 11.7 mg/dL, procalcitonin 0.2 ng/mL, new-onset atrial fibrillation on EKG, negative COVID-19 PCR test, and normal age-adjusted D-Dimer levels. Chest X-ray demonstrated bibasilar patchy airspace opacities predominantly involving the right lower lobe and echocardiogram revealed normal ejection fraction. She was started on empiric broad-spectrum antibiotic therapy with vancomycin and cefepime for suspected pneumonia with sepsis and the osimertinib was withheld temporarily. Over the next few days, her respiratory failure continued to worsen despite the antibiotics. Chest CT scan now demonstrated bilateral dense lower lobe consolidation with air bronchograms and new-onset bilateral pleural effusion but a decrease in the size of dominant lung mass. She was started on high-dose corticosteroids for suspected drug-induced pneumonitis and her symptoms improved significantly within 24 h of starting steroid therapy. Subsequently, all antibiotics were discontinued, and she was discharged home on corticosteroid taper and with osimertinib drug being held.

Repeat CT scan at 6 weeks from discharge revealed near-total resolution of the infiltrates and pleural effusions. Given the impressive response of patient's lung cancer to osimertinib, complete resolution of pulmonary symptoms without any further complications, and literature review supporting the successful reintroduction of the drug among some patients despite a history of pulmonary side effects, osimertinib was cautiously restarted at half the standard dose and gradually escalated to the full dose of 80 mg daily. The patient tolerated drug reintroduction well has remained asymptomatic, and continues to have antitumor benefits. Repeat CT scan at 6 weeks from discharge revealed near-total resolution of the infiltrates and pleural effusions. Given the impressive response of patient's lung cancer to osimertinib, complete resolution of pulmonary symptoms without any further complications, and literature review supporting the successful reintroduction of the drug among some patients despite a history of pulmonary side effects, osimertinib was cautiously restarted at half the standard dose and gradually escalated to the full dose of 80 mg daily. The patient tolerated drug reintroduction well has remained asymptomatic, and continues to have antitumor benefit.

Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216030/
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