A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum-and erlotinib-resistant adenocarcinoma of the lung Journal Article

Authors: Leighl, N. B.; Raez, L. E.; Besse, B.; Rosen, P. J.; Barlesi, F.; Massarelli, E.; Gabrail, N.; Hart, L. L.; Albain, K. S.; Berkowitz, L.; Melnyk, O.; Shepherd, F. A.; Sternas, L.; Ackerman, J.; Shun, Z.; Miller, V. A.; Herbst, R. S.
Article Title: A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum-and erlotinib-resistant adenocarcinoma of the lung
Abstract: 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. © 2010 by the International Association for the Study of Lung Cancer.
Keywords: adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; treatment response; aged; middle aged; cancer surgery; survival rate; major clinical study; overall survival; clinical trial; constipation; drug tolerability; fatigue; salvage therapy; erlotinib; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; gemcitabine; cancer patient; cancer radiotherapy; anorexia; adenocarcinoma; progression free survival; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; etoposide; nausea; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; antineoplastic activity; drug resistance, neoplasm; angiogenesis; cancer resistance; arthralgia; asthenia; coughing; drug fever; dyspnea; chemotherapy induced emesis; drug induced headache; lung adenocarcinoma; recombinant fusion proteins; multicenter study; urinary tract infection; aflibercept; peripheral edema; platinum; taxane derivative; navelbine; heart left ventricle ejection fraction; quinazolines; brain ischemia; organoplatinum compounds; epistaxis; pemetrexed; proteinuria; functional status; hemoptysis; hoarseness; central nervous system disease; dysphonia; posterior reversible encephalopathy syndrome; vegf inhibitor; bronchus rupture; musculoskeletal pain; tracheoesophageal fistula
Journal Title: Journal of Thoracic Oncology
Volume: 5
Issue: 7
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2010-07-01
Start Page: 1054
End Page: 1059
Language: English
DOI: 10.1097/JTO.0b013e3181e2f7fb
PUBMED: 20593550
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "Source: Scopus"
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MSK Authors
  1. Vincent Miller
    270 Miller