Regorafenib pulmonary toxicity: A case of cavitary lung disease and ARDS treated with infliximab.

Regorafenib-induced pneumonitis and acute respiratory distress syndrome (ARDS) are rare and poorly characterized toxicities. We describe a 43-year-old male with metastatic colorectal cancer who developed hypoxic respiratory failure after two cycles of regorafenib. Imaging revealed cavitary lung lesions and diffuse ground glass opacities. Despite antibiotics and high-dose corticosteroids, his condition deteriorated, requiring ICU admission and mechanical ventilation. Bronchoalveolar lavage revealed bacterial pathogens, and he was treated for pneumonia. After multidisciplinary discussion, he was assessed to have regorafenib-induced pneumonitis as a major driver of his respiratory failure, and after limited steroid response, infliximab was administered with marked respiratory improvement. However, he later developed fungal sepsis and died from refractory shock. This is the first reported case of regorafenib-induced pneumonitis and ARDS treated with infliximab and corticosteroids. The patient's transient response suggests overlap with immune-related pneumonitis mechanisms seen in tyrosine kinase and immune checkpoint inhibitor therapies. Further research is needed to clarify regorafenib's immunotoxicity and the role of advanced immunosuppressive therapies in managing pneumonitis.