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.

• Authors: Rodryg Ramlau, Vera Gorbunova, Tudor Eliade Ciuleanu, Silvia Novello, Mustafa Ozguroglu, Tuncay Goksel, Clarissa Baldotto, Jaafar Bennouna, Frances A Shepherd, Solenn Le-Guennec, Augustin Rey, Vincent Miller, Nicholas Thatcher, Giorgio Scagliotti
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 29 Pg. 3640-7 (Oct 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22965962 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• Taxoids
• aflibercept
• Docetaxel
• Platinum
• Receptors, Vascular Endothelial Growth Factor

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Confidence Intervals
• Disease-Free Survival
• Docetaxel
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Maximum Tolerated Dose
• Neoplasm Invasiveness (pathology)
• Neoplasm Staging
• Platinum (therapeutic use)
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Receptors, Vascular Endothelial Growth Factor
• Recombinant Fusion Proteins (therapeutic use)
• Risk Assessment
• Survival Analysis
• Taxoids (therapeutic use)
• Treatment Outcome