A Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung

• Published in: Journal of thoracic oncology Vol. 5; no. 7; pp. 1054 - 1059
• Main Authors: Leighl, Natasha B., Raez, Luis E., Besse, Benjamin, Rosen, Peter J., Barlesi, Fabrice, Massarelli, E., Gabrail, Nashat, Hart, Lowell L., Albain, Kathy S., Berkowitz, Lloyd, Melnyk, Ostap, Shepherd, Frances A., Sternas, Lars, Ackerman, Judie, Shun, Zhenming, Miller, Vincent A., Herbst, Roy S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2010; International Association for the Study of Lung Cancer
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adult; Aged; Angiogenesis; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Drug Resistance, Neoplasm; Erlotinib Hydrochloride; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Organoplatinum Compounds - administration & dosage; Quinazolines - administration & dosage; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins - therapeutic use; Salvage Therapy; Survival Rate; Treatment Outcome; VEGF inhibitor; Adenocarcinoma; VEGF inhibitor; Angiogenesis
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0b013e3181e2f7fb

Aflibercept (vascular endothelial growth factor [VEGF] trap), a recombinant fusion protein, blocks the activity of VEGF-A and placental growth factor and has demonstrated activity in pretreated patients with lung cancer in a phase I trial. This study evaluated the efficacy and safety of intravenous aflibercept in patients with platinum- and erlotinib-resistant lung adenocarcinoma. An open-label, single arm, multicenter trial was conducted, with the primary end point of response rate (modified RECIST). Additional endpoints included safety, duration of response, progression-free survival, and overall survival. Patients with platinum- and erlotinib-resistant lung adenocarcinoma were eligible. Aflibercept 4.0 mg/kg intravenous every 2 weeks was administered until progression of disease or intolerable toxicity. Ninety-eight patients were enrolled; 89 were evaluable for response. Median age was 60 years, 41% were men with Eastern Cooperative Oncology Group performance status 0/1/2 in 35/55/9% of patients. The overall response rate was 2.0%, (95% confidence interval, 0.2-7.2%). Median progression-free survival was 2.7 months, and overall was survival 6.2 months. Six- and 12-month survival rates were 54 and 29%, respectively. A median of four cycles was administered (range 1-22). Common grade 3/4 toxicities included dyspnea (21%), hypertension (23%), and proteinuria (10%). Two cases of grade 5 hemoptysis were reported, and one case each of tracheoesophageal fistula, decreased cardiac ejection fraction, cerebral ischemia, and reversible posterior leukoencephalopathy. Aflibercept has minor single agent activity in heavily pretreated lung adenocarcinoma, and is well tolerated, with no unexpected toxicities. Further studies evaluating aflibercept in lung cancer, in combination with chemotherapy and other targeted therapies, are ongoing.