Can You Establish the Cause of This Patient's Shortness of Breath?

Mr. B is a 56-year-old man diagnosed with metastatic HER2-positive gastroesophageal adenocarcinoma. He received front-line leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) and trastuzumab for 10 months before restaging imaging revealed progressive disease. He then received second-line trastuzumab deruxtecan. His treatment was complicated by several admissions felt to be unrelated to his cancer therapy. He was discharged after an episode of pneumonia on a steroid taper with prophylactic trimethoprim/sulfamethoxazole. Once he recovered, he was given a fourth dose of chemotherapy. About a week later, wheezes were noticed on physical exam, and he was given a 5-day course of levofloxacin. Around the same time, he also finished his steroid taper. Twelve days after his dose of chemotherapy, he presented to the emergency room with 3 to 4 days of progressive shortness of breath and dry cough following the completion of levofloxacin without symptom improvement. A CT scan showed increasing airspace opacities and multifocal areas of consolidation. Blood, nasal, and sputum cultures were negative. A bronchoscopy was performed that did not reveal findings concerning for capillaritis. He was ultimately diagnosed with drug-induced pneumonitis/interstitial lung disease (ILD). Mr. B continued to experience worsening hypoxic respiratory failure despite continuous IV steroids. He was discharged to an inpatient hospice facility where he passed away 2 weeks later. Drug-induced pneumonitis/ILD should be considered in all patients receiving trastuzumab deruxtecan who develop progressive shortness of breath or other respiratory complaints.