Nintedanib combined with anticoagulant therapy in advanced lung cancer complicated with pulmonary fibrosis and pulmonary embolism: two case reports and clinical decision-making analysis.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. With the development of targeted therapy and immunotherapy, the prognosis of patients with advanced non-small cell lung cancer has been significantly improved. However, the occurrence of comorbidities such as pulmonary fibrosis (PF) and pulmonary embolism (PE) significantly worsens the prognosis of these patients. Nintedanib is an effective antifibrotic drug, but its inhibition of vascular endothelial growth factor receptor may increase the risk of bleeding. Anticoagulant therapy is the cornerstone of PE treatment, and the combined use of nintedanib and anticoagulants may further increase the bleeding risk, which poses a clinical dilemma. At present, real-world data on the combined use of nintedanib and anticoagulants in patients with lung cancer complicated with PF and PE are scarce. Case presentation: We reported two cases of patients with advanced lung adenocarcinoma complicated with PF and PE. Case 1 was a 67-year-old male patient with left lung adenocarcinoma (cT2N2M1c IVB) complicated with idiopathic pulmonary fibrosis and acute PE. He had a history of hemoptysis after chemotherapy and was treated with nintedanib for antifibrosis before admission. After admission, nintedanib was temporarily discontinued due to the relative contraindication between anticoagulation therapy and bleeding. After the patient's condition stabilized, low-dose nintedanib was reinitiated, and the anticoagulant was switched to rivaroxaban orally after discharge. Follow-up showed no bleeding and the thrombosis disappeared. Case 2 was a 69-year-old male patient with right lung adenocarcinoma (cT4N3M1a IVA) with BRAF V600E and TP53 mutations, complicated with drug-related interstitial pneumonia and acute PE. He was treated with nintedanib combined with enoxaparin sodium. After the occurrence of mild hemoptysis, only the anticoagulant dose was adjusted without discontinuing nintedanib, and the bleeding symptoms were gradually relieved after discharge. Conclusion: The core contradiction in the treatment of advanced lung adenocarcinoma complicated with PF and PE is the balancing of bleeding risk between nintedanib antifibrotic treatment and anticoagulant therapy. Clinical decisions need to be based on individualized risk-benefit assessment. Individualized risk assessment and precise plan adjustment are key to improving the prognosis of these complex patients and providing practical references for similar clinical cases. Further studies are required in the future to confirm the safety of nintedanib when used in combination with anticoagulants.