Review: Bevacizumab is Safe in Broader Range of Patients Than Previously Thought

Non—small-cell lung cancer (NSCLC) represents approximately 85% of all lung cancers, and more than half of all cases of NSCLC are diagnosed at an advanced stage. Bevacizumab (Avastin and its FDA-approved biosimilar Mvasi), a vascular endothelial growth factor (VEGF) inhibitor is the only antiangiogenic agent approved for first-line treatment of NSCLC, but many patients are considered ineligible to receive the drug. A review recently published in Lung Cancer: Targets and Therapy describes patient selection for treatment with bevacizumab, and argues that bevacizumab has a good safety profile in patient subpopulations previously considered ineligible for treatment with the therapy.

While bevacizumab is generally safe and well tolerated in patients with NSCLC, bleeding in patients treated with the therapy—which may be related to inhibition of the endothelial repair process mediated by VEGF and tumor erosion of vessels—meant that the first randomized clinical trials of bevacizumab in NSCLC excluded patients with squamous histology, significant hemoptysis, tumors invading or abutting major blood vessels, central tumor localization, tumor cavitation, hemorrhage disorders, brain metastases, an Eastern Cooperative Oncology Group grade higher than 1, or an age of 75 or above.

These exclusion criteria, some researchers have suggested, may be too precautionary, and could lead to the inappropriate avoidance of bevacizumab therapy in patients who could benefit from the drug. For example, the authors point out, no statistically significant association has been found between baseline or on-treatment cavitation tumor and severe pulmonary hemorrhage incidence in patients treated with bevacizumab, nor has central tumor location been shown to be a consistent predictive factor for severe pulmonary hemorrhage. While major blood vessel infiltration and bronchial vessel infiltration, encasement, or abutting could predict pulmonary hemorrhage, their valuation is an individual assessment.

Furthermore, several studies, including the phase 2 PASSPORT trial, found that bevacizumab was safe and related to a low incidence of central nervous system hemorrhage in patients with NSCLC and brain metastases.

Retrospective data on bevacizumab in elderly patients with NSCLC yield a conflicting view; a subset analysis of the ECOG 4599 study showed that grade 3 and grade 4 adverse events were significantly more frequent in elderly subjects (87%) than in younger subjects (61%). However, in a retrospective analysis of 304 elderly patients participating in the AVAiL study, improved progression-free survival, without an impact on survival and with no significant toxicities, was observed.

At present, there exist no validated predictive biomarkers of response to treatment with bevacizumab, though recent studies suggest that biomarkers (including circulating levels of VEGF-A isoforms) could correlate with better clinical outcomes in patients with NSCLC treated with antiangiogenesis agents.

The authors conclude that the only absolute contraindications for bevacizumab are squamous histology and a history of clinically significant hemoptysis, and that age, performance status, brain metastases, and anticoagulation therapy do not affect patient eligibility. However, there exists a need for additional translational research into biomarkers predictive of treatment response in order to identify patients who could benefit from treatment with bevacizumab.