SUNITINIB IS OUT FOR BREAST CANCER

J Clin Oncol. 2012 Feb 13. [Epub ahead of print]

First-Line Treatment of Advanced Breast Cancer With Sunitinib in Combination With Docetaxel Versus Docetaxel Alone: Results of a Prospective, Randomized Phase III Study.

Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C.

Source

Jonas Bergh and Annelie Liljegren, Karolinska Institutet and University Hospital, Stockholm, Sweden; Jonas Bergh, University of Manchester, Paterson Institute for Cancer Research, Manchester, United Kingdom; Igor M. Bondarenko, Dnipropetrovsk City Multiple-Discipline Clinical Hospital No. 4, Dnipropetrovsk; Nataliya L. Voytko, Kyiv City Oncologic Hospital, Kyiv, Ukraine; Mikhail R. Lichinitser, National Cancer Research Center; Anatoly N. Makhson, City Oncology Clinical Hospital No. 62, Moscow, Russian Federation; Richard Greil, Oncology Center, Paracelsus Medical University Salzburg, Salzburg, Austria; Javier Cortes, Hospital General Universitario Vall D'Hebron, Barcelona, Spain; Alain Lortholary, Centre Catherine de Sienne, Nantes; Suzette Delaloge, Institut Gustave Roussy, Villejuif, France; Joachim Bischoff, Klinikum der Otto-von-Guericke Universität, Frauenklinik, Magdeburg, Germany; Arlene Chan, Mount Medical Centre, Perth, Australia; Xin Huang and Kenneth A. Kern, Pfizer Oncology, La Jolla, CA; and Carla Giorgetti, Pfizer Oncology, Milan, Italy.

Abstract

PURPOSETo investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer (ABC) versus docetaxel alone. PATIENTS AND METHODSIn this phase III study, patients were randomly assigned to open-label combination therapy (sunitinib 37.5 mg/d, days 2 to 15 every 3 weeks; and docetaxel 75 mg/m(2), day 1 every 3 weeks) or monotherapy (docetaxel 100 mg/m(2) every 3 weeks). Progression-free survival (PFS) was the primary end point.ResultsTwo hundred ninety-six patients were randomly assigned to combination therapy, and 297 patients were assigned to monotherapy. Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy, respectively (hazard ratio, 0.92; one-sided P = .265). The objective response rate (ORR) was significantly higher with the combination (55%) than with monotherapy (42%; one-sided P = .001). Duration of response was similar in both arms (7.5 months with the combination v 7.2 months with monotherapy). Median overall survival (OS) times were 24.8 and 25.5 months with combination therapy and monotherapy, respectively (one-sided P = .904). There were 107 deaths with the combination and 91 deaths with monotherapy. The frequency of common adverse events (AEs) was higher with the combination, as were treatment discontinuations caused by AEs. CONCLUSIONThe combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC. Sunitinib combination therapy may also have resulted in AEs that yield an unfavorable risk-benefit ratio. The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC.