Rapid-onset and fatal pneumonitis from trametinib treatment of non-small cell lung cancer: A case report

Abstract

Introduction: Lung cancer remains the leading cause of death in both men and women worldwide. Oral targeted therapy remains the recommended first-line approach for those with actionable mutations. The combination of trametinib and dabrafenib has shown durable responses as both a first line and second line treatment in patients with non-small cell lung cancer (NSCLC) with a BRAFV600E mutation. Respiratory complications with trametinib have rarely been documented, with an incidence of less than 2%. Case Report: A 58-year-old former female smoker who presented with dyspnea on exertion and was found to have a right hilar mass. The mass was biopsied and found to be a poorly differentiated carcinoma consistent with NSCLC. Tumor proportion score (TPS) was 100% for programmed death-ligand 1 (PD-L1) expression, and molecular analysis confirmed a BRAFV600E mutation. She was started on treatment with dabrafenib 150 mg twice daily with trametinib 2 mg once daily. After ten days, she developed fever followed by leukocytosis and hypoxia. Chest imaging was suggestive of pneumonitis, and she was initiated on high-dose steroids and antibiotics. Her cultures remained negative, though she was unable to be weaned from high-flow oxygen. She transitioned to hospice care several days later and subsequently passed in another 12 days. Conclusion: Trametinib-induced interstitial pneumonitis, while a relatively rare occurrence, can become rapidly life-threatening and should prompt immediate cessation of the medication followed by urgent supportive care measures.