Phase III Trial Evaluating the Addition of Bevacizumab to Endocrine Therapy As First-Line Treatment for Advanced Breast Cancer: The Letrozole/Fulvestrant and Avastin (LEA) Study

被引：97

作者：

Martin, Miguel ^{[1
]}

Loibl, Sibylle ^{[13
,14
]}

von Minckwitz, Gunter ^{[13
,14
]}

Morales, Serafin ^{[5
]}

Martinez, Noelia ^{[2
]}

Guerrero, Angel ^{[6
]}

Anton, Antonio ^{[7
]}

Aktas, Bahriye ^{[15
]}

Schoenegg, Winfried ^{[16
]}

Munoz, Montserrat ^{[8
]}

Angel Garcia-Saenz, Jose ^{[3
]}

Gil, Miguel ^{[10
]}

Ramos, Manuel ^{[11
]}

Margeli, Mireia ^{[9
]}

Carrasco, Eva ^{[4
]}

Liedtke, Cornelia ^{[17
,18
]}

Wachsmann, Grischa ^{[19
]}

Mehta, Keyur ^{[13
,14
]}

De la Haba-Rodriguez, Juan R. ^{[12
]}

机构：

[1] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, E-28040 Madrid, Spain

[2] Univ Hosp Ramon y Cajal, Madrid, Spain

[3] Univ Hosp Clin San Carlos, Madrid, Spain

[4] Grp Espanol Invest Canc Mama, Madrid, Spain

[5] Hosp Arnau de Vilanova Lerida, Lerida, Spain

[6] Valencian Inst Oncol, Valencia, Spain

[7] Univ Hosp Miguel Servet, Zaragoza, Spain

[8] Univ Hosp Clin & Prov, Barcelona, Spain

[9] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain

[10] Catalan Inst Oncol, Lhospitalet De Llobregat, Spain

[11] Ctr Oncol Galicia, La Coruna, Spain

[12] Univ Cordoba, Hosp Univ Reina Sofia, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain

[13] Neu Isenburg, German Breast Grp, Offenbach, Germany

[14] Sana Klinikum Offenbach, Offenbach, Germany

[15] Univ Womens Hosp Essen, Essen, Germany

[16] Med Practice Berlin, Berlin, Germany

[17] Univ Womens Hosp Munster, Munster, Germany

[18] Univ Hosp Lubeck, Lubeck, Germany

[19] Klinikum Boblingen, Boblingen, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 09期

关键词：

ENDOTHELIAL GROWTH-FACTOR; ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; FACTOR EXPRESSION; TUMOR-GROWTH; ANGIOGENESIS; COMBINATION; LETROZOLE; AUTOCRINE; CARCINOMA;

D O I：

10.1200/JCO.2014.57.2388

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET. Patients and Methods A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety. Results From 380 patients recruited (2007 to 2011), 374 were analyzed by intent to-treat (184 patients on ET and 190 patients on ET-B). Median age was 65 years, 270 patients (72%) had Eastern Cooperative Oncology Group performance status of 0, 178 patients (48%) had visceral metastases, and 171 patients (46%) and 195 patients (52%) had received prior chemotherapy or ET, respectively. Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.06; P = .126). ORR, CBR, and RD with ET versus ET-B were 22% versus 41% (P < .001), 67% versus 77% (P = .041), and 13.3 months versus 17.6 months (P = .434), respectively. TTF and OS were comparable in both arms. Grade 3 to 4 hypertension, aminotransferase elevation, and proteinuria were significantly higher in the ET-B arm. Eight patients (4.2%) receiving ET-B died during study or within 30 days of end of treatment. Conclusion The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer. (C) 2015 by American Society of Clinical Oncology

引用

页码：1045 / +

页数：11

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