Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: A randomized, controlled phase III trial Journal Article


Authors: Ramlau, R.; Gorbunova, V.; Ciuleanu, T. E.; Novello, S.; Ozguroglu, M.; Goksel, T.; Baldotto, C.; Bennouna, J.; Shepherd, F. A.; Le-Guennec, S.; Rey, A.; Miller, V.; Thatcher, N.; Scagliotti, G.
Article Title: Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: A randomized, controlled phase III trial
Abstract: Purpose: To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant human fusion protein targeting the vascular endothelial growth factor (VEGF) pathway, with or without docetaxel in platinum-pretreated patients with advanced or metastatic nonsquamous non-small-cell lung cancer. Patients and Methods: In this international, double-blind, placebo-controlled phase III trial, 913 patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n = 456) or IV placebo (n = 457), both administered every 3 weeks and in combination with docetaxel 75 mg/m 2. The primary end point was overall survival (OS). Other efficacy outcomes, safety, and immunogenicity were also assessed. Results: Patient characteristics were balanced between arms; 12.3% of patients had received prior bevacizumab. (Ziv-)Aflibercept did not improve OS (hazard ratio [HR], 1.01; 95% CI, 0.87 to 1.17; stratified log-rank P = .90). The median OS was 10.1 months (95% CI, 9.2 to 11.6 months) for (ziv-)aflibercept and 10.4 months (95% CI, 9.2 to 11.9 months) for placebo. In exploratory analyses, median progression-free survival was 5.2 months (95% CI, 4.4 to 5.6 months) for (ziv-)aflibercept versus 4.1 months (95% CI, 3.5 to 4.3 months) for placebo (HR, 0.82; 95% CI, 0.72 to 0.94; P = .0035); overall response rate was 23.3% of evaluable patients (95% CI, 19.1% to 27.4%) in the (ziv-)aflibercept arm versus 8.9% (95% CI, 6.1% to 11.6%; P < .001) in the placebo arm. Grade > 3 adverse events occurring more frequently in the (ziv-)aflibercept arm versus the placebo arm were neutropenia (28.0% v 21.1%, respectively), fatigue (11.1% v 4.2%, respectively), stomatitis (8.8% v 0.7%, respectively), and hypertension (7.3% v 0.9%, respectively). Conclusion: The addition of (ziv-)aflibercept to standard docetaxel therapy did not improve OS. In exploratory analyses, secondary efficacy end points did seem to be improved in the (ziv-)aflibercept arm. The study regimen was associated with increased toxicities, consistent with known anti-VEGF and chemotherapy-induced events. © 2012 by American Society of Clinical Oncology.
Keywords: vasculotropin; adult; cancer survival; controlled study; treatment outcome; treatment response; aged; disease-free survival; survival analysis; major clinical study; overall survival; fatigue; neutropenia; bevacizumab; erlotinib; placebo; advanced cancer; cancer combination chemotherapy; diarrhea; drug dose reduction; drug efficacy; drug safety; hypertension; side effect; gemcitabine; cancer patient; outcome assessment; lymph node metastasis; neoplasm staging; prospective studies; progression free survival; multiple cycle treatment; bleeding; lung non small cell cancer; randomized controlled trial; stomatitis; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; proportional hazards models; drug administration schedule; weight reduction; dexamethasone; dose-response relationship, drug; risk assessment; docetaxel; asthenia; drug hypersensitivity; dyspnea; febrile neutropenia; lung embolism; confidence interval; confidence intervals; drug fatality; dysphagia; liver metastasis; lung metastasis; statistical significance; recombinant fusion proteins; immunogenicity; aflibercept; platinum; neoplasm invasiveness; platinum derivative; taxoids; headache; vinca alkaloid; hazard ratio; phase 3 clinical trial; maximum tolerated dose; taxane derivative; dna topoisomerase inhibitor; navelbine; double blind procedure; double-blind method; drug treatment failure; digestive system perforation; wound healing impairment; epistaxis; pemetrexed; proteinuria; bone necrosis; dysgeusia; venous thromboembolism; log rank test; pleura metastasis; bone metabolism; decreased appetite; dysphonia; kaplan-meier estimate; exploratory research; digestive system fistula; lacrimation disorder; chemotherapy induced nausea and vomiting
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 29
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-10-10
Start Page: 3640
End Page: 3647
Language: English
DOI: 10.1200/jco.2012.42.6932
PROVIDER: scopus
PUBMED: 22965962
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Vincent Miller
    251 Miller