Review on the clinical use of eribulin mesylate for the treatment of breast cancer

Aseyev, Olexiy; Ribeiro, Joana; Cardoso, Fátima

doi:10.1517/14656566.2016.1146683

Cited by 25 publications

(20 citation statements)

References 55 publications

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“…In this context, there is a keen interest to develop therapeutic alternatives with high cytotoxicity against MDR cancer cells. The recent FDA-approval of eribulin mesylate that overcome the MDR cell phenotype 41 , 42 illustrates this effort. In our study, PP-13 was shown to overcome efflux-mediated chemoresistance and could thus present a strong advantage over vinca-alkaloids that are actively effluxed by MRP1 and P-glycoprotein transporters or over taxanes that are exported by P-glycoprotein and MRP2 16 .…”

Section: Discussionmentioning

confidence: 99%

Identification of pyrrolopyrimidine derivative PP-13 as a novel microtubule-destabilizing agent with promising anticancer properties

Gilson

Josa-Prado

Beauvineau

et al. 2017

Sci Rep

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Despite the emergence of targeted therapies and immunotherapy, chemotherapy remains the gold-standard for the treatment of most patients with solid malignancies. Spindle poisons that interfere with microtubule dynamics are commonly used in chemotherapy drug combinations. However, their troublesome side effects and the emergence of chemoresistance highlight the need for identifying alternative agents. We performed a high throughput cell-based screening and selected a pyrrolopyrimidine molecule (named PP-13). In the present study, we evaluated its anticancer properties in vitro and in vivo. We showed that PP-13 exerted cytotoxic effects on various cancer cells, including those resistant to current targeted therapies and chemotherapies. PP-13 induced a transient mitotic blockade by interfering with both mitotic spindle organization and microtubule dynamics and finally led to mitotic slippage, aneuploidy and direct apoptotic death. PP-13 was identified as a microtubule-targeting agent that binds directly to the colchicine site in β-tubulin. Interestingly, PP-13 overcame the multidrug-resistant cancer cell phenotype and significantly reduced tumour growth and metastatic invasiveness without any noticeable toxicity for the chicken embryo in vivo. Overall, PP-13 appears to be a novel synthetic microtubule inhibitor with interesting anticancer properties and could be further investigated as a potent alternative for the management of malignancies including chemoresistant ones.

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Section: Discussionmentioning

confidence: 99%

Identification of pyrrolopyrimidine derivative PP-13 as a novel microtubule-destabilizing agent with promising anticancer properties

Gilson

Josa-Prado

Beauvineau

et al. 2017

Sci Rep

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“…3 Eribulin mesylate (EM, Halaven ® , E7389), a synthetic analog of the marine natural product halichondrin B, isolated from the Japanese marine sponge Halichondria okadai, is a nontaxane microtubule dynamics inhibitor, with a different site and mechanism of action as compared to taxanes and vinca-alcaloïds. 4 EM was approved by the US Food and Drug Administration (FDA) on November 15, 2010, and by the French regulatory authorities on March 22, 2012, based on the results of the pivotal open-label phase III randomized study EMBRACE. 5 The study compared EM monotherapy vs. treatment of physician's choice (TPC) in MBC patients previously treated with anthracyclines, taxanes and, for most patients, capecitabine.…”

Section: Introductionmentioning

confidence: 99%

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Jacot

Heudel

Fraisse

et al. 2019

Intl Journal of Cancer

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Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real‐life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression‐free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti‐HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth‐line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth‐line). No significant difference was reported in second‐line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd‐line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real‐world database, HER2‐negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2‐targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti‐HER2 therapies addition in this setting still needs to be defined.

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“…Eribulin mesylate is a synthetic analogue of halichondrin B that inhibits the dynamics of the microtubules in the cell leading to cell‐cycle arrest and apoptosis . Eribulin is active, with manageable safety profile in metastatic breast cancer patients previously treated with taxanes and anthracyclines .…”

Section: Introductionmentioning

confidence: 99%

Safety of eribulin as third-line chemotherapy in HER2-negative, advanced breast cancer pre-treated with taxanes and anthracycline: OnSITE study

et al. 2019

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Eribulin is active and safe in heavily pre‐treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre‐treated HER2‐negative ABC, programmed to receive eribulin as third‐line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression‐free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug‐related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1‐5.9) and median OS was 13.6 months (11.8‐not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in <5 baseline CTC patients compared to ≥5 baseline CTC patients (13.1 months [95% CI: 11.8‐not reached] vs 12.5 months [95% CI: 7.6‐not reached]; P = 0.045). A significant correlation (P = 0.0129) was observed between CTC levels at cycle 2 and death when CTCs were analyzed using cox regression. Eribulin chemotherapy is effective and safe as third line in advanced HER2‐negative breast cancer. CTC levels correlate with overall survival.

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Review on the clinical use of eribulin mesylate for the treatment of breast cancer

Cited by 25 publications

References 55 publications

Identification of pyrrolopyrimidine derivative PP-13 as a novel microtubule-destabilizing agent with promising anticancer properties

Identification of pyrrolopyrimidine derivative PP-13 as a novel microtubule-destabilizing agent with promising anticancer properties

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Safety of eribulin as third-line chemotherapy in HER2-negative, advanced breast cancer pre-treated with taxanes and anthracycline: OnSITE study

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