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

Martín, Miguel; Loibl, Sibylle; Minckwitz, Gϋnter von; Morales, Serafín; Martín, Miguel; Guerrero, Ángel; Antón, Antonio; Aktas, Bahriye; Schoenegg, Winfried; Muñoz, Montserrat; García-Sáenz, José Á.; Gil, Miguel Gil; Ramos, Manuel; Margelı́, Mireia; Carrasco, Eva; Liedtke, Cornelia; Wachsmann, Grischa; Mehta, Keyur; Haba-Rodríguez, J.R. de la

doi:10.1200/jco.2014.57.2388

Cited by 113 publications

(84 citation statements)

References 23 publications

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“…A recent meta-analysis showed that exemestane and everolimus in combination was more efficacious than fulvestrant alone in patients with relapsed BC previously treated with nonsteroidal AIs [63] . Unfortunately, in women with ER+ BC, the addition of an anti-vascular endothelial growth factor (bevacizumab) to fulvestrant or letrozole did not change the resistance of the tumor to ET, and failed to improve PFS or OS [64] .…”

Section: Endocrine Therapy and Molecular-target Therapymentioning

confidence: 99%

Current medical treatment of estrogen receptor-positive breast cancer

Lumachi

Santeufemia

Basso

2015

WJBC

167

126

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Approximately 80% of breast cancers (BC) are estrogen receptor (ER)-positive and thus endocrine therapy (ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of (1) ovarian function suppression (OFS), usually obtained using gonadotropinreleasing hormone agonists (GnRHa); (2) selective estrogen receptor modulators or down-regulators (SERMs or SERDs); and (3) aromatase inhibitors (AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs (i.e. , tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ , especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs (i.e. , fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs (i.e. , anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors (palbociclib) and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.

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Section: Endocrine Therapy and Molecular-target Therapymentioning

confidence: 99%

Current medical treatment of estrogen receptor-positive breast cancer

Lumachi

Santeufemia

Basso

2015

WJBC

167

126

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“…This trial has many differences compared to the LEA trial (21). In the LEA trial, patients with advanced disease were endocrine treatment-naïve.…”

Section: Patients (N=65)mentioning

confidence: 99%

“…It is used in metastatic breast cancer in biologically non-aggressive forms of the disease and in more aggressive forms after a maximal chemotherapy response has been achieved (5). For the firstline therapy of advanced breast cancer, an aromatase inhibitor combined with bevacizumab was investigated in a phase III LEA trial (21). Similarly, as reported in chemotherapy trials, the endocrine therapy-bevacizumab combination resulted in higher response rates but failed to demonstrate statistically significant improvements in both PFS and OS compared to endocrine-therapy alone.…”

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confidence: 99%

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer

Tiainen

Tanner

Lahdenperä

et al. 2016

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Abstract. Aim Metastatic breast cancer remains an incurable disease (1, 2). In Finland, nearly 5,000 patients are diagnosed with invasive breast cancer every year, and the incidence has increased steadily over the past decades. The Finnish cancer registry data from 2014 shows that 815 women died of metastatic breast cancer, which was the most common cause of cancer death in women (3). In the CONCORD-2 study, a central analysis of population-based registry data worldwide for cancer survival was conducted, and the results were published in The Lancet in November 2014. The study reported that the treatment results of breast cancer in Finland are among the best in the world. The 5-year-survival rate of patients with breast cancer in Finland was 86.8% [95% confidence interval (CI)=85.9-87.7%) from [2005][2006][2007][2008][2009], and was the highest in Northern Europe (4). However, new treatment options for advanced human epidermal growth factor receptor 2 (HER2)-negative disease are rare, and the overall survival benefit observed in these patients is modest (5, 6). For this reason, advanced HER2-negative breast cancer is a treatment challenge worldwide.Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial cell proliferation by blocking the binding of vascular endothelial growth factor A (VEGFA) to its receptor, therefore inhibiting tumor angiogenesis (7). Bevacizumab improves the outcomes of cytotoxic treatment in many metastatic malignancies, including colorectal, kidney, lung and ovarian cancer (8-11). There has been much debate about the status of bevacizumab treatment in metastatic breast cancer. Currently, the European Medicines Agency has only approved bevacizumab when combined with paclitaxel or capecitabine in a first or second-line setting (http://www.e ma.europa.eu/ema/). In 2011, the US Food and Drug Administration revoked its accelerated approval of a breast cancer indication for bevacizumab due to the lack of a benefit in breast cancer overall survival and, in addition, due to the potentially life-threatening side-effects (http://www.fda.gov/). 6431Τhis article is freely accessible online. In locally advanced and metastatic breast cancer, taxanebased treatment (docetaxel or paclitaxel), either in combination with another agent or as single-agent, therapy is considered one of the most effective choices for first-line treatment (5, 12), when cytotoxic treatment is needed. Combining bevacizumab with chemotherapy has been studied in certain phase III studies (13)(14)(15)(16)(17)(18). Most of these studies investigated the benefit of bevacizumab combined with a taxane. Furthermore, other chemotherapy regimens have been explored, including capecitabine, anthracycline, vinorelbine and gemcitabine. Adding bevacizumab has led to higher response rates and longer progression-free survival (PFS) throughout the trials, but no significant differences in overall survival (OS) have yet been observed.In addition to chemotherapy options, bevacizumab can also be combined with endocri...

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“…The combination of BEV plus an endocrine therapy with letrozole compared to letrozole alone in postmenopausal metastatic breast cancer patients has failed to improve progression-free survival in the LEA trial [15]. Recently, however, the first results of the phase III Cancer and Leukemia Group B (CALGB) trial 40503 have been presented.…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapy of HER2-Negative Breast Cancer

Schütz

Domschke

Schneeweiß³

2016

Oncol Res Treat

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Personalized and targeted treatments are the most discussed topics in oncology. However, how much personalized medicine is standard of care nowadays and how much is part of our hope for a better future? So far, only a few targeted therapies are available in daily practice for the treatment of human epidermal growth factor receptor 2 (HER2)-negative breast cancer. And even for these few targeted agents - besides those targeting the estrogen receptor (ER) for endocrine treatment - thus far, predictive factors are missing. There are many new drugs and strategies under evaluation but, unfortunately, they are being developed without any cross-comparison. What drug will we choose for which patient in the future? Without answering this question oncologists will not be able to individualize treatment. Predictive factors for every new splendid drug are eagerly needed before it comes to an approval.

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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

Abstract: 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.

Cited by 113 publications

References 23 publications

Current medical treatment of estrogen receptor-positive breast cancer

Current medical treatment of estrogen receptor-positive breast cancer

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer

Targeted Therapy of HER2-Negative Breast Cancer

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