EP1.14-37 Anlotinib-Induced Broncho-Pericardial/Pleural Fistula in Patients Suffering from Lung Cancer (First Report)

Anlotinib is an small molecule inhibitor of multiple receptor tyrosine kinases, with inhibitory effects on tumor angiogenesis, and approved in China for treatment of patients with non-small cell lung cancer (NSCLC) who have undergone progression after≥2 lines of chemotherapy. The occurrence of bronchial fistula related to anlotinib has not been reported yet. We presented 2 cases of NSCLC patients with bronchial fistula after treatment with anlotinib. Case 1: A 69-year-old male diagnosed central squamous cell lung carcinoma(CSCLC) of the left (stage IV) on July 2018, who refused chemotherapy but treated with anlotinib for 3 months, aggravated with short breath, with CT indicating broncho-pericardial fistula. After catheter was set into pericardium and drained for 5 days, CT showed significant reduction of gas and pericardium partially conglutinated. Case 2: 63-year-old male diagnosed CSCLC of the right (EGFR 19del) in 2016, with a history of diabetes, who successively received 2 lines of chemotherapy, target therapy, radiotherapy, shifted to anlotinib in August 2018 for 4 months, then aggravated with coughing pyohemosputum and fever, with CT indicating broncho-pleural fistula. After performed a closed thoracic drainage and anti-bacterium therapy, the patient improved and drainage decreased. Two cases developed bronchial fistula during the treatment of anlotinib alone, suggesting that the adverse effects mainly related to the antiangiogenics effect of it and causing ischemic necrosis. Other possible factors include: ①central lung cancer,②squamous cell carcinoma,③cachexia,④multi-line treatment,⑤long diameter of tumor≥5cm) and cavity formation,⑥radiotherapy,⑦accompanied with underlying diseases easy to complicated with infection, such as diabetes. Although the incidence of bronchial fistula caused by anlotinib in NSCLC is extremely rare, it seriously affects the quality of life and overall survival of patients. Therefore, we need to use it selectively and make a close observation of the high-risk patients.