From the Guidelines
Bevacizumab is generally safe in patients with stage IV non-small cell lung cancer (NSCLC) and treated brain metastases, with no significant increase in pulmonary adverse reactions, as evidenced by the Study of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous NSCLC (PASSPORT) study 1.
Key Points
- The PASSPORT study found no reported grade 1 to 5 CNS hemorrhages in patients with advanced NSCLC and treated brain metastases receiving bevacizumab 1.
- The Study of Avastin in Combination With Chemotherapy for Treatment of Colorectal Cancer and Non-small Cell Lung Cancer (ARIES) prospective, observational cohort study also found no episodes of CNS bleeding in 150 patients with CNS metastases 1.
- The risk of pulmonary hemorrhage is low, with no reports of severe (grade 3) pulmonary hemorrhage among patients receiving anticoagulation in the bevacizumab treatment groups 1.
- Regular monitoring of respiratory symptoms and pulmonary function is essential throughout treatment with bevacizumab.
Management and Prevention
- Immediate discontinuation of bevacizumab is recommended if severe pulmonary hemorrhage occurs.
- Careful patient selection is crucial to avoid treating those with high-risk features, such as squamous cell histology in lung cancer, central tumor location, cavitation, and prior radiation therapy.
- Patients with an ECOG PS of 0 to 1 can be safely treated with bevacizumab, but data on patients with an ECOG PS of 2 or those requiring anticoagulation are limited 1.
From the Research
Pulmonary Adverse Reactions to Bevacizumab
- Bevacizumab has been associated with various pulmonary adverse reactions, including pulmonary hemorrhage, pulmonary embolism, and pulmonary thrombosis 2, 3, 4, 5, 6
- A study using the Japanese Adverse Drug Event Report database found that approximately 20% of adverse events associated with bevacizumab were thromboembolic events, with pulmonary embolism being the most frequently reported 2
- Another study found that bevacizumab is associated with a significantly increased risk of thromboembolism development in non-small cell lung cancer (NSCLC) patients, with a dose-toxicity relationship 5
- However, a meta-analysis found that bevacizumab may not increase the risk of pulmonary embolism in cancer patients 6
- Predictive factors for pulmonary hemorrhage in patients with NSCLC treated with bevacizumab include squamous histology and a history of grade ≥ 2 hemoptysis 3
- Patients with NSCLC should be monitored for signs of pulmonary adverse reactions, including pulmonary hemorrhage and pulmonary embolism, during bevacizumab therapy 2, 3, 4
Risk Factors and Management
- Risk factors for pulmonary adverse reactions to bevacizumab include underlying disease process, squamous histology, and history of hemoptysis 3
- Management of pulmonary adverse reactions includes monitoring for signs of onset, discontinuing bevacizumab in case of severe adverse events, and medically managing hypertension and thromboembolic events 2, 4
- Patients should be monitored for proteinuria every three to four weeks, and bevacizumab should be discontinued with persistent proteinuria of >2+ 4
- Bevacizumab should be started at least four weeks after surgery or discontinued for at least six to eight weeks before elective surgery to minimize the risk of bleeding or impaired wound healing 4