Fatal interstitial lung disease associated with Crizotinib pathologically confirmed by percutaneous lung biopsy in a patient with ROS1-rearranged advanced non-small-cell lung cancer: a case report

Background: Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood. Case presentation: We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died. Conclusions: The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.