Phase II Genomics Study of Ixabepilone as Neoadjuvant Treatment for Breast Cancer

Baselga, José; Zambetti, Milvia; Llombart-Cussac, Antonio; Manikhas, Georgy; Kubista, E.; Steger, G.; Махсон, А. Н.; Tjulandin, Sergei; Ludwig, H; Verrill, Mark; Ciruelos, Eva; Egyházi, Suzanne; Xu, Lian; Zerba, Kim E.; Lee, Hye-Rim; Clark, Edwin; Galbraith, Susan

doi:10.1200/jco.2007.14.2646

Cited by 101 publications

(69 citation statements)

References 35 publications

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“…A newer agent, ixabepilone, has been evaluated in subsets of patients with triple-negative metastatic breast cancer, in phase II and phase III studies [16,17]. Like the other agents discussed, there is evidence of activity, but it is difficult to assess the relative value of this drug compared with the others in this cohort beyond stating simply that it is active (Table 2).…”

Section: Limitations Of Current Treatment Strategies For Triple-negatmentioning

confidence: 99%

Triple-Negative Breast Cancer: An Unmet Medical Need

2011

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Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The metastatic potential in triple-negative breast cancer is similar to that of other breast cancer subtypes, but these tumors are associated with a shorter median time to relapse and death. One important goal is therefore the identification of prognostic factors and markers to reliably select high and low risk subsets of patients with triple-negative disease for different treatment approaches of subtypes with differential responsiveness to specific agents. However, a reliable prognostic marker has been elusive, and markers have been inconsistently useful. For example, epidermal growth factor receptor (EGFR) has been studied, but there is still a lack of agreement on a standard assay or cutoff for EGFR expression levels with respect to prognosis. Similarly, because triple-negative status is sometimes used as a surrogate for basal-like breast cancer, specific basal markers have been explored. Indeed, trials designed to accrue patients with basal-like breast cancer using ER/PR and HER-2 negativity may provide only an approximation of the triple-negative population and are sometimes reanalyzed using more specific indicators like CK 5/6, EGFR status, and others, again marred by discordances. Chemotherapy remains the mainstay of treatment of triple-negative breast cancer, but important limitations still need to be overcome in the next few years if any significant clinical strides are to be made. Current treatment strategies for triple-negative disease include anthracyclines, taxanes, ixabepilone, platinum agents, and biologic agents. More recently, EGFR inhibition has been proposed as a therapeutic mechanism in triple-negative breast cancer, again with mixed results. Agents that target poly-(ADP-ribose) polymerase and androgen receptors have also been proposed in these patients or subsets of them, and ongoing trials should result in definitive guidance with respect to the value of these agents in triple-negative disease.Triple-negative breast cancer is clearly a distinct clinical subtype, from the perspective of both ER and HER-2 expression, but further subclassification is needed. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple-negative breast cancer. This article will review the clinical problem of triple-negative disease, potential prognostic factors, demonstrated efficacy of currently available therapeutic options, and new potential therapies. The Oncologist 2011;16(suppl 1):1-11

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Section: Limitations Of Current Treatment Strategies For Triple-negatmentioning

confidence: 99%

Triple-Negative Breast Cancer: An Unmet Medical Need

2011

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“…Under this perspective a trial testing erlotinib along with chemotherapy in the neoadjuvant setting in women with TNBC is underway (NCT00491816). Finally, cetuximab is currently tested in combination with ixabepilone that has shown efficacy in a previous neoadjuvant trial in TNBC patients [63] in the NCT01097642 clinical trial.…”

Section: Novel Agents In the Neoadjuvant Treatment Of Tnbcmentioning

confidence: 99%

The recent progress of neoadjuvant chemotherapy in triple negative breast cancer: A short review

Liontos

Karageorgopoulou²,

Michalaki³

et al. 2015

JST

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Triple negative breast cancer (TNBC) encompasses tumors that do not express either the estrogen receptor (ER) or the progesterone receptor (PR) and also do not overexpress the Human Epidermal growth factor Receptor 2 (HER2). This is a heterogenous group of tumors that significantly overlaps with both basal-like tumors and BRCA1/BRCA2 mutationassociated tumors. TNBC is highly aggressive in nature and exhibits worse prognosis than the other subtypes of breast cancer, despite its increased chemosensitivity. Neoadjuvant chemotherapy (NACT) is a treatment option regularly incorporated in clinical practice to improve subsequent surgical management. In parallel, allows rating of the pathological compete response (pCR) which is associated with the prognosis of these patients and evaluates the efficacy of the applied treatment as well. Platinum-based regimens and novel targeted therapies have shown some benefit in TNBC, though an unmet need for improved therapeutic strategies in this patient population still remains. In this review, the latest progresses in NACT in TNBC are discussed, along with the improved understanding of molecular targets and useful biomarkers in this group of patients.

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“…22,[31][32][33][34][35] Trials at several institutions are expanding the investigation of ixabepilone in patients with primary untreated breast cancer. For instance, in an ongoing phase II study, the efficacy and tolerability of neoadjuvant ixabepilone is being compared with paclitaxel when administered after doxorubicin and cyclophosphamide in patients with early breast cancer.…”

Section: Ixabepilone In Primary Untreated Breast Cancermentioning

confidence: 99%

“…15 Furthermore, as a single agent or in combination with capecitabine, ixabepilone has demonstrated clinical efficacy across the spectrum of breast cancer treatment in a number of studies. [22][23][24][25][26][27][28][29] This article reviews the clinical evidence that supports the use of ixabepilone in the treatment of various stages of breast cancer.…”

Section: Dovepressmentioning

confidence: 99%

“…22 Patients with tumors at least 3 cm in diameter were administered an intravenous (IV) infusion of ixabepilone at 40 mg/m 2 over 3 hours on day 1 of a 21-day cycle for up to 4 cycles prior to surgery. Surgery was followed by anthracycline-based adjuvant chemotherapy, radiotherapy, or tamoxifen, as indicated.…”

Section: Ixabepilone In Primary Untreated Breast Cancermentioning

confidence: 99%

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Ixabepilone development across the breast cancer continuum: a paradigm shift

Ibrahim¹

2010

CMR

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Abstract:The epothilone analog ixabepilone exhibits reduced susceptibility to several important tumor survival mechanisms that limit the efficacy of taxanes and anthracyclines. As a single agent, ixabepilone has shown promise in metastatic breast cancer when anthracyclines, taxanes, or capecitabine have failed; and in early-stage breast cancer that is taxane-naïve or has previously received taxanes in the adjuvant or metastatic setting. Compared with capecitabine alone, ixabepilone used in combination with capecitabine in patients previously treated with and resistant to anthracyclines and taxanes produced a 25% reduction in the risk of disease progression. Triple-negative tumors showed particular susceptibility to this doublet. Ixabepilone has also demonstrated efficacy as first-line therapy in combination with targeted agents such as bevacizumab and trastuzumab. Ongoing investigations should provide insight as to how this agent could be integrated into treatment of early-stage disease. In clinical studies, toxicities with ixabepilone were manageable and reversible through dose reduction or delay, even in patients with extensive or heavily-pretreated disease. Thus, ixabepilone represents a useful addition to the therapeutic options available for advanced breast cancer, and it may extend progression-free survival in patients with limited treatment options.

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Phase II Genomics Study of Ixabepilone as Neoadjuvant Treatment for Breast Cancer

Abstract: indicate an inverse relation between ER expression levels and ixabepilone sensitivity. Neoadjuvant ixabepilone demonstrated promising activity and a manageable safety profile in patients with invasive breast tumors.

Cited by 101 publications

References 35 publications

Triple-Negative Breast Cancer: An Unmet Medical Need

Triple-Negative Breast Cancer: An Unmet Medical Need

The recent progress of neoadjuvant chemotherapy in triple negative breast cancer: A short review

Ixabepilone development across the breast cancer continuum: a paradigm shift

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