Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial

Láng, István; Brodowicz, Thomas; Ryvo, Larisa; Kahán, Zsuzsanna; Greil, Richard; Beslija, S.; Stemmer, Salomon M.; Kaufman, Bella; Zvirbule, Zanete; Steger, G.; Melichar, Bohuslav; Pieńkowski, Tadeusz; Sîrbu, Daniela; Messinger, Diethelm; Zielinski, Christoph

doi:10.1016/s1470-2045(12)70566-1

Cited by 85 publications

(54 citation statements)

References 17 publications

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“…The response rates previously reported with the bevacizumabtaxane combination range from 36.9% to 64.1% compared to 21.2-46.4% with single taxane therapy (13,14,31). Similarly, good responses were achieved in this study.…”

Section: Discussionsupporting

confidence: 74%

“…The contributing factor was underlying diverticulosis in our patient. Additionally, high-grade proteinuria and hypertension were observed, which are known side-effects of bevacizumab (13)(14)(15)(16)(17)31). Caution should be exercised when treating patients with known risk factors for the use of bevacizumab, namely a history of thromboembolic events, cardiovascular disease or risk factors for abdominal infection and fistula, among others.…”

Section: Patients (N=65)mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 74%

Section: Patients (N=65)mentioning

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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“…Other randomized controlled trials, AVADO (2) and RIBBON-1 (3), showed that the addition of bevacizumab to chemotherapy led to a statistically significant improvement in overall response and PFS in the first-line treatment of MBC. The subsequent trial TURANDOT (4) further demonstrated that the E2100 trial was not an outlier; it reproduced the considerable improvement of PFS by up to 11 months with the administration of weekly paclitaxel plus bevacizumab. All trials (E2100, AVADO, RIBBON-1, RIBBON-2 and TURANDOT) (1-5) showed significant PFS benefits for patients with MBC when bevacizumab was added to chemotherapy.…”

Section: Introductionmentioning

confidence: 93%

Window of opportunity: A new insight into sequential bevacizumab and paclitaxel in two cases of metastatic triple-negative breast cancer

Chen

Lin

Wang

2015

Experimental and Therapeutic Medicine

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Abstract. Bevacizumab, an antiangiogenic monoclonal antibody against vascular endothelial growth factor, was designed to normalize tumor vasculature and reduce intratumoral pressure. It can create a 'normalization window' during which the cancer can be attacked the most effectively, and the effects of chemotherapeutic drugs are enhanced. Representative trials (E2100, AVADO, RIBBON-1, RIBBON-2 and TURANDOT) have shown that the addition of bevacizumab to chemotherapy has significant benefits on progression-free survival for metastatic breast cancer, but not on overall survival. The present study describes two patients with metastatic triple-negative breast cancer who received 6 courses of bevacizumab-containing chemotherapy. Each course comprised 5-7.5 mg/kg bevacizumab administered on days 1 and 15, and 20-24 h after bevacizumab delivery, 80 mg/m 2 paclitaxel was administered for 3 weeks on days 2, 9 and 16, followed by 1 week of rest. Following sequential treatment with bevacizumab and paclitaxel, the results of computed tomography showed that the tumors were rapidly reduced in size. Based on the imaging findings from three-dimension power Doppler ultrasonography in one of the breast cancer patients who received neoadjuvant chemotherapy with bevacizumab, the possible timing of the normalization window was 20-24 h after the administration of bevacizumab. The normalization window may provide an opportunity to enhance the effect of chemotherapy with the aid of bevacizumab. IntroductionIn the E2100 trial, it was revealed that the initial treatment of metastatic breast cancer (MBC) with bevacizumab plus paclitaxel (BT regimen) greatly prolonged progression-free survival (PFS) from 5.9 to 11.8 months, but not overall survival (OS), as compared with paclitaxel alone (1). Other randomized controlled trials, AVADO (2) and RIBBON-1 (3), showed that the addition of bevacizumab to chemotherapy led to a statistically significant improvement in overall response and PFS in the first-line treatment of MBC. The subsequent trial TURANDOT (4) further demonstrated that the E2100 trial was not an outlier; it reproduced the considerable improvement of PFS by up to 11 months with the administration of weekly paclitaxel plus bevacizumab. All trials (E2100, AVADO, RIBBON-1, RIBBON-2 and TURANDOT) (1-5) showed significant PFS benefits for patients with MBC when bevacizumab was added to chemotherapy. However, PFS intervals were observed to differ among trials; furthermore adverse effects were reported including 1% mortality associated with bevacizumab (RIBBON-1 and AVADO).Hypoxia is a key component in the regulation of angiogenesis (6). Vascular endothelial growth factor (VEGF) blockade can normalize tumor vasculature and reduce intratumoral pressure, thereby enhancing the effectiveness of chemotherapeutic drugs (7,8). The changes in the normalization effects over time were further demonstrated by Vokoc et al, who observed that an anti-VEGF2 antibody can normalize tumor vasculature, which includes the pruning of immature vasculature, and ...

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“…All trials of bevacizumab in mbca have reported a significant improvement in pfs in favour of bevacizumab [7][8][9][10][11] (Table i). To date, the only randomized clinical trial designed to assess os as a primary objective was the turandot noninferiority trial (bevacizumab-capecitabine vs. bevacizumabpaclitaxel) 11 .…”

Section: Regulatory Contextmentioning

confidence: 99%

“…To date, the only randomized clinical trial designed to assess os as a primary objective was the turandot noninferiority trial (bevacizumab-capecitabine vs. bevacizumabpaclitaxel) 11 . The only results currently available for that trial are preliminary, and in the planned interim efficacy analysis, they showed no clinically relevant difference in the os primary endpoint (Table i) 11 .…”

Section: Regulatory Contextmentioning

confidence: 99%

Use of Bevacizumab as a First-Line Treatment for Metastatic Breast Cancer

et al. 2015

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ObjectiveDuring clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca.MethodsA panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab.ResultsThe subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training.ConclusionsThis expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

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Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial

Cited by 85 publications

References 17 publications

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

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

Window of opportunity: A new insight into sequential bevacizumab and paclitaxel in two cases of metastatic triple-negative breast cancer

Use of Bevacizumab as a First-Line Treatment for Metastatic Breast Cancer

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