Abstract Background Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) widely used as first-line therapy in EGFR-mutant non-small cell lung cancer due to its favorable efficacy. However, osimertinib-induced pneumonitis remains an underreported, potentially life-threatening complication. The mechanism behind pulmonary toxicity from EGFR inhibitors is not fully understood. However, since EGFR is expressed on type II alveolar cells and aids repair, inhibition may impair healing and worsen injury. According to the National Cancer Institute’s Common Terminology Criteria for Adverse Events, severe cases of grade IV pneumonitis are rare but clinically significant and may cause life-threatening respiratory compromise. Case Presentation A 59-year-old male with newly diagnosed stage IV EGFR-mutant lung adenocarcinoma was initiated on osimertinib. Within two weeks, he developed progressive dyspnea. He was hypoxemic with 85% oxygen saturation on room air. Chest imaging showed diffuse ground glass opacities with prominent interstitial markings and scattered consolidative infiltrates. He was admitted for acute hypoxemic respiratory failure (AHRF) with presumed pneumonia. Despite broad-spectrum antibiotics, his AHRF rapidly worsened and he was intubated on hospital day two. Bronchoscopy showed non-purulent bloody secretions, and lavage excluded diffuse alveolar hemorrhage. All blood, respiratory, and viral cultures remained negative throughout hospital course. Sixty milligram methylprednisolone were initiated for suspected drug-induced pneumonitis, which led to marked clinical and radiographic improvement. He was extubated on day six and weaned to two liters of oxygen by day twelve. His AHRF fully recovered after discharge following completion of a prolonged prednisone taper. Discussion This case illustrates a fulminant presentation of osimertinib-induced pneumonitis leading to AHRF requiring mechanical ventilatory support. While radiographic and mild cases are described in literature, severe presentations requiring mechanical ventilation are rarely reported. Retrospective studies have shown drug-induced pneumonitis from osimertinib typically develops within the first 2-8 weeks, often presenting with subacute symptoms, such as mild cough or dyspnea. In this case, he developed rapidly progressive AHRF within 12 days of starting osimertinib. This early and severe manifestation highlights the potential for atypical and underrecognized presentations. Prompt discontinuation of osimertinib and early initiation of corticosteroids resulted in significant clinical improvement. Clinicians should maintain a high index of suspicion for osimertinib-induced pneumonitis, even within the first two weeks of treatment, especially in patients presenting with worsening respiratory symptoms unresponsive to antibiotics. Conclusion Osimertinib-induced pneumonitis can present with rapidly progressive and life-threatening respiratory failure. Severe cases may be underreported, highlighting the need for early recognition and intervention. This abstract is funded by: None
Tore et al. (Fri,) studied this question.