Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial

American Society of Clinical Oncology (ASCO) - Tập 27 Số 20 - Trang 3312-3318 - 2009
Bernard Escudier1,2,3,4,5,6,7, Tim Eisen1,2,3,4,5,6,7, Walter M. Stadler1,2,3,4,5,6,7, Cezary Szczylik1,2,3,4,5,6,7, Stéphane Oudard1,2,3,4,5,6,7, Michael Staehler1,2,3,4,5,6,7, Sylvie Négrier1,2,3,4,5,6,7, Christine Chevreau1,2,3,4,5,6,7, Apurva A. Desai1,2,3,4,5,6,7, Frédéric Rolland1,2,3,4,5,6,7, Tomasz Demkow1,2,3,4,5,6,7, Thomas Powles1,2,3,4,5,6,7, Martin Gore1,2,3,4,5,6,7, Sibyl Anderson1,2,3,4,5,6,7, Gloria Hofilena1,2,3,4,5,6,7, Minghua Shan1,2,3,4,5,6,7, Carol Peña1,2,3,4,5,6,7, Chetan Lathia1,2,3,4,5,6,7, Ronald M. Bukowski1,2,3,4,5,6,7
1Bayer HealthCare Pharmaceuticals, Montville, NJ; and
2Baylor Charles A. Sammons Cancer Center, Dallas, TX
3Centrum Onkologii, Warsaw, Poland
4Cleveland Clinic Taussig Cancer Center, Cleveland, OH
5Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
6From the From Institut Gustave Roussy, Villejuif; Hôpital Européen Georges Pompidou, Paris; Centre Léon Bérard, Lyon; Institut Claudius Regaud, Toulouse; Centre René Gauducheau, Saint-Herblain, France; Cambridge Research Institute, Cambridge; Royal Marsden Hospital, Surrey, United Kingdom; Military School of Medicine; Centrum Onkologii, Warsaw, Poland; Urologische Klinik und Poliklinik Klinikum der Universität Großhadern Ludwig-Maximilian-Universität, München, Germany; University of Chicago, Chicago, IL;...
7University of Chicago, Chicago, IL

Tóm tắt

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.

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