Background and objective Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor
that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of
anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes.
Methods We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and
PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and
"fistula."
Results Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated
the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk
factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced
age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally
located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment
especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophagotracheobronchial
fistula. Six patients all died within 6 months.
Conclusion Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment
side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close
observation of high-risk patients.