RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Brufsky, Adam; Hurvitz, Sara A.; Perez, Edith A.; Swamy, Raji; Valero, Vicente; O’Neill, Vincent; Rugo, Hope S.

doi:10.1200/jco.2010.34.1255

Cited by 361 publications

(209 citation statements)

References 13 publications

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“…Although anthracyclines and taxanes are the representative agents used as standard chemotherapy in the adjuvant setting, these agents have also been used in several cases of MBC (1)(2)(3)(4) and selecting therapeutic regimens in this setting may be difficult for physicians. In cases of hormone-insensitive tumors, or cases of hormone-sensitive tumors that exhibit resistance to endocrine therapy, cytotoxic agents that have not been previously administered, or taxanes in combination with molecular-targeted agents, are potential candidates (4)(5)(6)(7)(8)(9). Recently, taxanes in combination with bevacizumab, which targets the tumor vasculature to reduce blood supply to the tumors (7-9), or eribulin, which is an analogue of halichondrin B targeting tubulin in tumor cells, have demonstrated favorable efficacy in improving the prognosis of patients with MBC (10).…”

Section: Introductionmentioning

confidence: 99%

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Kontani

Hashimoto

Murazawa

et al. 2016

Molecular and Clinical Oncology

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Abstract.The survival of patients with metastatic breast cancer (MBC) has not improved, despite recent advances in therapeutic strategies. This is mainly due to the fact that cytotoxic agents cannot be administered over a long period, even if they exhibit favorable activity, due to treatment-related side effects or acquisition of tumor resistance to the administered agents. Thus, the development of therapeutic strategies that may be used over a long time period is required to improve survival. We assessed the availability and clinical outcomes of metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of cytotoxic drugs. A total of 80 patients with MBC received chemotherapy in the metastatic setting, and the clinicopathological factors and clinical outcomes were retrospectively compared between 52 patients who received metronomic regimens and 28 patients who received other cytotoxic regimens. As regards clinical outcomes, the median time-to-treatment failure (TTF) and overall survival (OS) were significantly longer in the metronomic group compared with those in the non-metronomic group (TTF, 15 vs. 4 months, P=0.0001; and OS, 53 vs. 28 months P=0.0012, respectively). In the metronomic group, none of the 18 patients who responded to the regimen had triple-negative (TN) cancer (17 had luminal-type tumors and 1 had a human epidermal factor receptor 2-type tumor). Furthermore, TTF and OS were significantly longer in patients with non-TN cancer compared with those in patients with TN cancer in the metronomic group (TTF, 16 vs. 7 months, P=0.0014; and OS, 108 vs. 20 months, P=0.000007, respectively). The proportion of patients who experienced treatment-related adverse events was significantly lower in the metronomic group compared with that in the non-metronomic group (36.5 vs. 61.5%, respectively; P=0.038). In conclusion, metronomic chemotherapy is a viable option for luminal-type MBC in terms of effectiveness and minimal toxicity, regardless of metastatic sites or prior treatment. However, an alternative treatment is required for TN cancer.

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Section: Introductionmentioning

confidence: 99%

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Kontani

Hashimoto

Murazawa

et al. 2016

Molecular and Clinical Oncology

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“…Studies that demonstrate decreased tumor uptake of small molecule chemotherapeutics following bevacizumab administration and a lack of a survival benefit typically dose above 10 mg/ kg. [27][28][29] Others have demonstrated decreased tumor uptake using radiolabelled antibodies with and without a 5 mg/kg dose of bevacizumab dosed once one day prior to and 2 additional bevacizumab treatments following antibody therapy. 30 Timing of bevacizumab therapy may limit the vascular remodeling required to improve therapeutic delivery.…”

Section: Discussionmentioning

confidence: 99%

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

Chung

Warram²,

Day

et al. 2015

Cancer Biology & Therapy

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“…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%

“…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.…”

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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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RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Abstract: The combination of bevacizumab with commonly used chemotherapies improved PFS in the second-line treatment of patients with HER2-negative metastatic breast cancer, with a safety profile comparable with that in prior phase III studies.

Cited by 361 publications

References 13 publications

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

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

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