Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial.
By B. Escudier, T. Eisen, W. Stadler, C. Szczylik, S. Oudard, M. Staehler, S. Négrier, C. Chevreau, A. Desai, F. Rolland and 9 more. Journal of Clinical Oncology, 2009
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PURPOSE Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. PATIENTS AND METHODS Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. RESULTS The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib. CONCLUSION Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine, Sociology and Political Science
View Paper: https://www.semanticscholar.org/paper/76c2bb693c4a3e018854b0742ea570a467cdba00
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Citations in the corpus
- Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. (2010, background): “15).(16) In both trials, there was substantial patient cross over to subsequent active therapy, likely contributing to the lack of a demonstrable survival advantage.”
- Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions (2014, background): “patients crossing over to sorafenib were excluded from the analysis [10].”
- Ten years of anti-vascular endothelial growth factor therapy (2016, background): “1) , demonstrated that VEGFA Tyr kinase inhibitors (RTKIs) sunitinib (Sutent; Pfizer) 19 and sorafenib (Nexavar; Bayer and Onyx Pharmaceuticals) 20 , as well as others, are currently approved for use in various cancers.”