Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 25; no. 30; pp. 4743 - 4750
• Main Authors: Herbst, Roy S., O'Neill, Vincent J., Fehrenbacher, Louis, Belani, Chandra P., Bonomi, Philip D., Hart, Lowell, Melnyk, Ostap, Ramies, David, Lin, Ming, Sandler, Alan
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.10.2007; Lippincott Williams & Wilkins
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma, Bronchiolo-Alveolar - drug therapy; Adenocarcinoma, Bronchiolo-Alveolar - pathology; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Disease-Free Survival; Erlotinib Hydrochloride; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Pemetrexed; Pneumology; Quinazolines - administration & dosage; Survival Rate; Taxoids - administration & dosage; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Relapse; Quinazoline derivatives; Lung cancer; Monoclonal antibody; non-small cell lung carcinoma; Epidermal growth factor receptor; Bevacizumab; Cancerology; Phase II trial; Bronchus disease; Antagonist; Protein-tyrosine kinase; Lung disease; Drug combination; Treatment resistance; Respiratory disease; Enzyme; Transferases; Treatment efficiency; Enzyme inhibitor; Malignant tumor; Chemotherapy; Vascular endothelium growth factor; Erlotinib; Combined treatment; Comparative study
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2007.12.3026

Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile. A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS). All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen. One hundred twenty patients were randomly assigned and treated. No unexpected adverse events were noted. Fewer patients (13%) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone (24%) or bevacizumab-chemotherapy (28%) arms. The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1%. Although not statistically significant, relative to chemotherapy alone, the risk of disease progression or death was 0.66 (95% CI, 0.38 to 1.16) among patients treated with bevacizumab-chemotherapy and 0.72 (95% CI, 0.42 to 1.23) among patients treated with bevacizumab-erlotinib. One-year survival rate was 57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy compared with 33.1% for chemotherapy alone. Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting. No unexpected safety signals were noted. The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials. The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group.