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

被引：216

作者：

Bergh, Jonas ^{[1
,2
,3
]}

Bondarenko, Igor M. ^{[4
]}

Lichinitser, Mikhail R. ^{[6
]}

Liljegren, Annelie ^{[1
,2
]}

Greil, Richard ^{[8
]}

Voytko, Nataliya L. ^{[5
]}

Makhson, Anatoly N. ^{[7
]}

Cortes, Javier ^{[9
]}

Lortholary, Alain ^{[10
]}

Bischoff, Joachim ^{[12
]}

Chan, Arlene ^{[13
]}

Delaloge, Suzette ^{[11
]}

Huang, Xin ^{[14
]}

Kern, Kenneth A. ^{[14
]}

Giorgetti, Carla ^{[15
]}

机构：

[1] Karolinska Inst, S-17176 Stockholm, Sweden

[2] Univ Hosp, S-17176 Stockholm, Sweden

[3] Univ Manchester, Paterson Inst Canc Res, Manchester, Lancs, England

[4] Dnipropetrovsk City Multiple Discipline Clin Hosp, Dnepropetrovsk, Ukraine

[5] Kyiv City Oncol Hosp, Kiev, Ukraine

[6] Natl Canc Res Ctr, Moscow, Russia

[7] City Oncol Clin Hosp 62, Moscow, Russia

[8] Paracelsus Med Univ Salzburg, Ctr Oncol, Salzburg, Austria

[9] Hospi Gen Univ Vall DHebron, Barcelona, Spain

[10] Ctr Catherine Sienne, Nantes, France

[11] Inst Gustave Roussy, Villejuif, France

[12] Klinikum Otto von Guericke Univ, Frauenklin, Magdeburg, Germany

[13] Mt Med Ctr, Perth, WA, Australia

[14] Pfizer Oncol, La Jolla, CA USA

[15] Pfizer Oncol, Milan, Italy

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 09期

关键词：

TYROSINE KINASE INHIBITOR; GROWTH-FACTOR; BEVACIZUMAB; SU11248; METASTASIS; TRIAL; CAPECITABINE; PACLITAXEL; CARCINOMA; INVASION;

D O I：

10.1200/JCO.2011.35.7376

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To 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 Methods In 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/m2 every 3 weeks). Progression-free survival (PFS) was the primary end point. Results Two 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. Conclusion The 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. J Clin Oncol 30: 921-929. (C) 2012 by American Society of Clinical Oncology

引用

页码：921 / 929

页数：9

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