S3887 A Case of Trastuzumab Deruxtecan Induced Colitis

Introduction: Trastuzumab deruxtecan (TDX-d) targeting human epidermal growth factor receptor 2 (HER2) was introduced as salvage therapy for metastatic/unresectable HER2-positive and HER2-negative breast cancer. A 2022 meta-analysis confirmed known adverse events including drug-related colitis. Phase 1 trials note colitis as a rare event. To the best of our knowledge, this is the first reported case outside a clinical trial of TDX-d associated colitis. Case Description/Methods: A 49-year-old woman with recurrent, metastatic triple negative breast cancer presented with diarrhea and encephalopathy after TDX-d initiation. She was admitted for hypovolemic shock, requiring ventilator support and renal replacement. She had pancytopenia, severe neutropenia, kidney injury, and liver injury. Infectious workup was negative. Computed tomography scan showed pancolitis. She developed hematochezia and colonoscopy had extensive ulceration. Pathology revealed chronic colitis suspicious for drug-induced colitis and without cytomegalovirus or ischemia. TDX-d was discontinued. Methylprednisolone (initially 40 mg orally daily up to 60 mg twice daily) failed to provide improvement. Cyclosporine (2 mg/kg IV to 100 mg orally twice daily) was initiated with diarrhea improvement/hematochezia resolution, however, symptoms recurred 15 days later. She was transitioned to infliximab (10 mg/kg intravenous) and received 2 doses 2 weeks apart, however, her diarrhea and inflammation persisted. Unfortunately, in the setting of refractory colitis, deconditioning and advancing disease with brain metastasis, she was transitioned to comfort care. Discussion: Drug induced colitis is a known complication of many medications, including irinotecan and deruxtecan. Deruxtecan can cause apoptotic death, and the drug class is associated with injury at the intestinal lining. The mechanism of TDX-d induced colitis is unclear. For those on TDX-d, abdominal pain and hematochezia should raise suspicion for drug-induced colitis. Although unsuccessful in our case, TNF-a inhibition is a highly effective treatment for steroid-resistant drug-induced colitis. IL-6 inhibition may treat immune checkpoint inhibitor- associated colitis. When drug-induced colitis is suspected, diagnosis and severity should be endoscopically confirmed and the causal agent discontinued. If colitis is severe/persistent, systemic glucocorticoids are first-line, and alternative immunosuppression such as those used above can be considered. In severe cases, surgical evaluation may be indicated.