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

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.