Eribulin In Metastatic Breast Cancer Research Articles

Real-world effect of bevacizumab and eribulin on metastatic breast cancer using a propensity score matching analysis.

Bevacizumab and eribulin are novel agents for the treatment of HER2-negative metastatic breast cancer (MBC); however, the choice between bevacizumab and eribulin for MBC can be difficult. The present study aimed to compare two treatment strategies, eribulin followed by bevacizumab and paclitaxel (BEV + PTX) versus BEV + PTX followed by eribulin, to determine whether the order of administration affects the outcome of MBC in the real world. A total of 180 patients who started BEV + PTX and eribulin treatment for HER2-negative MBC from August 2011 to June 2018 were selected. Of these, 84 patients were treated with both BEV + PTX and eribulin sequentially. To evaluate the influence of the sequential order, the efficacy of BEV + PTX followed by eribulin (B-E arm) was compared to treatment with the reverse sequence (E-B arm). The propensity score matching method (PSMA) was used to improve the robustness of the findings from the present study. A total of 60 cases analyzed received BEV + PTX or eribulin as either first- or second-line treatment. In the entire cohort, the median time to failure of strategy (TFS) was 16.8 and 9.9 months in the B-E and E-B arms, respectively [hazard ratio (HR)=0.515, 95% CI 0.298-0.889, P=0.017). A similar HR was derived from PSMA for TFS. Using PSMA, TFS was 16.9 and 9.9 months in the B-E and E-B arms, respectively (HR=0.491, 95% CI 0.253-0.952, P=0.031). These results suggested that when both bevacizumab and eribulin are administered, bevacizumab should be administered first and eribulin should be administered later to ensure the most effective use of each drug.

Eribulin Treatment for Patients with Metastatic Breast Cancer: The UK Experience – A Multicenter Retrospective Study

Introduction: This study examined real-world data from patients who received eribulin for metastatic breast cancer (MBC) collected from 14 hospitals across the UK. Methods: Anonymized data were collected retrospectively from patients with MBC who had received eribulin. The data included the hormone-receptor status, histological diagnosis, age, prior chemotherapy, response to eribulin, progression-free survival (PFS), and overall survival (OS). Results: Among 577 patients analyzed, the median age was 56 years, and most patients (73%) were estrogen-receptor positive. The median OS was 288 days (95% confidence interval [CI]: 261–315), and the PFS was 117 days (95% CI: 105–129). The median OS was higher among older patients (≥65 vs. <65 years: 325 days [95% CI: 264–385] vs. 285 days [95% CI: 252–317]; p = 0.028). The median OS was also higher in patients who received eribulin after fewer prior lines of chemotherapy (≤2 vs. >2 prior: 328 days [95% CI: 264–385] vs. 264 days [95% CI: 229–298]; p = 0.042). Discussion/Conclusion: These retrospective data suggest that eribulin can be successfully used in older patients with MBC. Eribulin treatment was more effective in earlier-line settings, which, while predictable, supports consideration of eribulin as a second-line treatment option.

Effectiveness of combination with eribulin in third line of chemotherapy for triple negative breast cancer (case report)

In most cases triple negative breast cancer is characterized by an aggressive course of disease and early development of resistance to chemotherapy. Thereafter, the late-line treatment choice, usually after anthracyclines and taxanes, is problematic due to the limited amount of effective and low-toxic cytostatics. In our opinion, in this situation the use of eribulin which possesses unique antitumor action mechanisms is a good option. An illustrative case of a pronounced antitumor effect of eribulin in metastatic breast cancer with triple negative phenotype resistant to previous lines of chemotherapy is presented.

Average duration of prior treatment lines predicts clinical benefit to eribulin chemotherapy in patients with metastatic breast cancer

PurposeThe aim of this study was to identify factors associated with progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC) treated with eribulin in a real-world setting, to improve information provision in those considering treatment.MethodsPatients treated with eribulin for MBC at The Christie NHS Foundation Trust, Manchester, UK, between August 2011 and December 2018 were included (n = 439). Data were collected by retrospective review of medical records and electronic prescribing systems. Factors such as biological subtype, distant recurrence-free interval, previous lines of chemotherapy and the ‘average duration of previous treatment lines’ (ADPT) (calculated as: (date of initiation of eribulin–date of MBC) / the number of previous treatment lines in the metastatic setting) were evaluated for prognostic impact using Cox proportional hazards regression.ResultsIn the full cohort, the median PFS and OS were 4.1 months (95% CI 3.7–4.4) and 8.6 months (95% CI 7.4–9.8), respectively. Outcomes were significantly inferior for those with triple-negative breast cancer (TNBC) (n = 92); PFSTNBC: 2.4 months (95% CI 2.1–3.0), p = < 0.001 and OSTNBC: 5.4 months (95% CI 4.6–6.6), p = < 0.001. ADPT was the only factor other than subtype significantly associated with PFS and OS. Longer ADPT was also significantly associated with PFS and OS in those with TNBC. For example, women in the lowest ADPT tertile (< 5.0 months) achieved a median OS of only 4.3 months, whereas those in the upper ADPT tertile (> 8.7 months) had a median OS of 12.1 months (p = 0.004).ConclusionOur results indicate that the ADPT lines is an important factor when predicting the outcome with eribulin chemotherapy in a palliative setting and that quantitative guidance on the likely PFS and OS with treatment can be provided using ADPT. Validation in additional cohorts is warranted.

Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

BackgroundTreatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile.MethodsWe conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy.FindingsWe consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients.InterpretationMetronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305

BackgroundThe recommended starting dose of eribulin in patients with hepatic impairment is based on the Child-Pugh score, largely informed by a pharmacokinetic study of 18 patients. In the pivotal studies of eribulin in metastatic breast cancer (Study 301 and Study 305 [EMBRACE]), entry criteria and dose modifications were based on liver-function test (LFT) results rather than Child-Pugh score. In populations such as patients with metastatic breast cancer, in which metastatic infiltration is the predominant cause of hepatic impairment, using Child-Pugh score may be problematic; in clinical practice, it has been more common for oncologists to make dosing decisions based on LFTs. To address this, the effects of abnormal baseline LFT results on eribulin efficacy and safety were investigated.MethodsIn this pooled post hoc analysis, 1062 patients who were randomized to receive eribulin in Studies 301 and 305 were divided into 4 groups: (A) no elevated LFT results (no liver impairment); (B) increased levels of aspartate aminotransferase and/or alanine aminotransferase; (C) decreased albumin and/or increased levels of aspartate aminotransferase and/or alanine aminotransferase but not increased bilirubin; and (D) increased bilirubin. Patients were subcategorized by presence of liver metastasis. Drug exposure, dose intensity, and treatment-emergent adverse events (TEAEs) were analyzed.ResultsEribulin mesylate mean dosage was 0.82 (group A)–0.65 mg/m2/week (group D). Group D had shorter treatment, more dose reductions/delays, more TEAEs leading to dose modifications, and numerically lower objective response rates and clinical benefit rates versus groups A–C. TEAE rates leading to dose modification were similar between group D (45.5%) and groups A–C (range, 43.5–54.9%) in the absence of liver metastases, but higher in group D (91.3%) compared with groups A–C (range, 41.7–54.3%) if liver metastases were present.ConclusionsMild elevations in bilirubin levels were associated with increased toxicity and a greater requirement for dose modifications. Based both on these study data and existing recommendations, we propose a novel scheme to guide initial dose selection in patients with metastatic breast cancer and hepatic impairment that is based on LFTs rather than Child-Pugh score.

Abstract PS4-20: Low levels of interleukin-6 at baseline were significantly associated with improved overall survival of patients treated with eribulin for locally advanced or metastatic breast cancer

Abstract (Background)Eribulin, a non-taxane inhibitor of microtubule dynamics, is a unique chemotherapy agent for locally advanced or metastatic breast cancer (MBC). The treatment has been demonstrated to extend overall survival (OS) without extending progression-free survival (PFS). This effect seems to result from the suppression of epithelial-mesenchymal transition (EMT) and improvement of the hypoxic microenvironment by vascular normalization induced by eribulin, directly or indirectly. In a previous study, we identified that high absolute lymphocyte count (ALC) at the baseline was significantly associated with longer OS in the eribulin group, but not in the treatment of physician’s choice (TPC) group, in the phase III EMBRACE trial (Miyoshi et al., Breast Cancer, 2020). These results strongly suggest an association between eribulin efficacy and immune response. Therefore, we focused on serum levels of immune and inflammatory cytokines,which are expected to have greater utility as a predictive factor for eribulin than ALC. Interleukin (IL) 6, an inflammatory cytokine associated with cancerprogression, and soluble interleukin-2 receptor (sIL-2R), a receptor of IL-2 released from various immune cells including T cells, B cells, and natural killer cells, were selected for the investigation. (Patients and methods)A total of 44 patients treated with eribulin for MBC were recruited for the study. We examined the predictive values of IL-6 and sIL-2R in addition to the neutrophil-to-lymphocyte ratio (NLR) and ALC at baseline. The cutoff values of NLR and ALC were set at 3.0 and 1500/μL, respectively. We used the normal ranges of IL-6 (4.0 pg/mL) and sIL-2R (474 U/mL) as cutoff values. (Results)The OS of patients with low NLR (n=28) and high ALC (n=17) were significantly longer than that of patients with high NLR (n=16, p=0.0287) and low ALC (n=27, p=0.0234). There were no significant associations between PFS and NLR or ALC (p=0.0852 and p=0.2231, respectively). Patients with normal IL-6 levels (n=17) had significantly longer PFS (p=0.0023) and OS (p=0.0013) than those with elevated IL-6 levels (n=27). Regarding sIL-2R, patients with normal sIL-2R levels (n=18) had longer OS (p=0.0483) than those with elevated sIL-2R levels (n=26), but their PFS was similar (p=0.2435). Multivariate analysis showed that IL-6 levels were only significantly associated with OS (hazard ratio, 0.093; 95% confidence interval, 0.012-0.720; p=0.0106). There was no significant association between IL-6 levels and NLR or ALC. (Conclusion and discussion)Patients treated with eribulin demonstrated a significantly longer OS if their baseline IL-6 levels were within the normal range. This predictive efficacy for eribulin was more accurate than that of NLR or ALC. As there was no significant association between IL-6 levels and NLR or ALC, IL-6 appears to predict whether the tumor microenvironment is favorable or unfavorable for eribulin treatment, mediated through different mechanisms. Therefore, IL-6 levels may be useful for selecting patients who will benefit from the administration of eribulin in terms of improved OS. Citation Format: Ayako Bun, Natsuko Inoue, Yoshimasa Miyagawa, Reiko Fukui, Yukie Fujimoto, Tomoko Higuchi, Atsushi Sata, Hiromi Ozawa, Michiko Imamura, Yasuo Miyoshi. Low levels of interleukin-6 at baseline were significantly associated with improved overall survival of patients treated with eribulin for locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-20.

A nationwide, multicenter retrospective study on the effectiveness and safety of eribulin in Korean breast cancer patients (REMARK)

PurposeApproval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study. MethodsPatients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) by intravenous infusion for 2–5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs). ResultsThe safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common. ConclusionReal-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.

Efficacy of eribulin for metastatic breast cancer based on localization of specific secondary metastases: a post hoc analysis

Prior pooled analysis of eribulin studies (301 and 305) indicated eribulin prolonged overall survival (OS) in patients with locally advanced/metastatic breast cancer (MBC) regardless of visceral or nonvisceral disease. This hypothesis-generating post hoc analysis examined the efficacy of eribulin according to the location of metastatic sites at baseline in 1864 pretreated patients with locally advanced/MBC from studies 301 and 305. Analyses included OS, progression-free survival (PFS), and objective response rate; OS and PFS were also analyzed according to estrogen-receptor status. Eribulin appeared efficacious in patients with locally advanced/MBC, irrespective of the location of metastases at baseline. A nominally significant difference in OS in favor of patients randomized to eribulin compared with control in patients with bone, lymph node, and chest wall/breast/skin metastases at baseline was observed. Additionally, a difference in OS was also seen in patients with liver metastases randomized to eribulin versus control (median: 13.4 versus 11.3 months, respectively; hazard ratio, 0.84 [95% CI: 0.72, 0.97]). Results of this exploratory analysis suggest that eribulin may be efficacious for the treatment of locally advanced/MBC for patients with bone, liver, lung, lymph node, and chest wall/breast/skin metastases.

Utility of the Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio for Predicting Survival in Patients with Metastatic Breast Cancer on Eribulin: A Real-World Observational Study

Introduction: Previous studies have suggested that the efficacy of eribulin is influenced by the activity of antitumor immunity of patients. Absolute lymphocyte count (ALC) and the neutrophil/lymphocyte ratio (NLR) are easily available parameters associated with the immunological status of patients. Objective: Here we tried to classify patients’ immunological status by using the scatter plot of ALC and NLR, and investigated its utility for predicting survival among patients with metastatic breast cancer receiving eribulin. Methods: The medical records of 125 patients who received eribulin for metastatic breast cancer at our hospital between July 2011 and April 2019 were retrospectively reviewed. Uni- and multivariate analyses were performed to determine the association between baseline ALC/NLR and progression-free survival (PFS)/overall survival (OS). The cutoff values for ALC and NLR were determined using scatter plot analysis. Results: The entire cohort was classified into immunologically favorable (ALC ≥1,500/µL, 30 patients), intermediate (ALC <1,500/µL, NLR <5.0, 76 patients), and unfavorable (NLR ≥5.0, 19 patients) groups. Univariate analysis showed significant differences in PFS and OS between the groups, whereas multivariate analysis revealed that ALC ≥1,500/µL and NLR ≥5.0 were independent predictors of PFS, with adjusted hazard ratios (95% CI) of 0.57 (0.33–0.99) and 1.78 (1.00–3.15), respectively. NLR ≥5.0 was also associated with worse OS (adjusted hazard ratio: 0.55; 95% CI 0.35–0.88; p = 0.013). Conclusions: Among patients with metastatic breast cancer receiving eribulin, survival outcomes were well stratified according to baseline peripheral blood ALC and NLR. Accordingly, high ALC and NLR can be used as predictive markers for longer disease control and worse survival, respectively.

Abstract P1-10-30: Survival benefit of eribulin for metastatic breast cancer depends on absolute lymphocyte count and neutrophil-lymphocyte ratio in peripheral blood

Abstract Background and Aims: Eribulin is a cytotoxic anti-cancer agent targeting microtubule dynamics, which improves the prognosis of patients with metastatic breast cancer. Preclinical studies have shown that eribulin enhances anti-tumor immunity by inhibiting regulatory T cells and M2 macrophages. Along with advances of immunotherapy for breast cancer, there has been growing interest in such immunologic effects of eribulin. Here we investigated the association between the immunological status of peripheral blood and survival outcomes in patients receiving eribulin for metastatic breast cancer. Methods: Medical records of 125 patients who received eribulin for metastatic breast cancer at Hiroshima City Hiroshima Citizens Hospital between July 2011 and April 2019 were retrospectively reviewed. We collected the data on patients’ baseline characteristics, laboratory tests and clinical courses. Absolute lymphocyte count (ALC) and neutrophil-lymphocyte ratio (NLR) in peripheral blood at the start of treatment with eribulin were calculated, and their association with progression-free survival (PFS) and overall survival (OS) were analyzed with log-rank test. The cutoff values for ALC and NLR were determined based on their distribution in this cohort. Subgroup analyses by breast cancer subtypes were also conducted. Results: The mean age was 57 years (range, 28-88). Eighty (64%) and 14 (11.2%) patients were positive for hormone receptors and HER2 overexpression. One hundred and ten patients (88%) had received one or more lines of chemotherapy for metastatic disease. We divided the entire cohort into three groups, using the cutoff values of 1500 /µL for ALC and 5 for NLR. Accordingly, 30 patients (24%) had favorable immune status (i.e., ALC ≥1500 /µL), whereas immune systems were considered to be suppressed (i.e., NLR ≥5) in 19 patients (15.2%); the rest 76 patients (60.8%) had neutral immune status (i.e., ALC &amp;lt;1500 /µL and NLR &amp;lt;5). Overall, ALC ≥1500 /µL was significantly associated with better PFS (hazard ratio, 0.55; 95% CI, 0.35-0.88; p=.013). In contrast, NLR ≥5 were significantly associated with worse PFS (hazard ratio, 1.92; 95% CI, 1.11-3.32; p=.019) and OS (hazard ratio, 4.26; 95% CI, 2.29-7.91; p&amp;lt;.001). These trends in relationship between ALC/NLR and survival outcomes were consistent across subgroups. Conclusions: The potential role of immune status of peripheral blood, such as ALC ≥1500 /µL and NLR ≥5, in predicting the efficacy of eribulin for metastatic breast cancer was suggested. Selecting patients with favorable immune status will be important to make the best use of eribulin. Citation Format: Ayako Ueno, Shoichiro Ohtani, Kensuke Kawasaki, Mitsuya Ito, Takanori Kin, Reina Maeda. Survival benefit of eribulin for metastatic breast cancer depends on absolute lymphocyte count and neutrophil-lymphocyte ratio in peripheral blood [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-30.

Abstract P2-15-12: Effect of Bevacizumab and Eribulin for metastatic breast cancer in the real world evaluated using the propensity score matching analysis (PSMA) and inverse probability of treatment weighting analysis (IPTWA)

Abstract Background: Bevacizumab (BEV) + Paclitaxel (PTX) and Eribulin represent the most frequently agents for the treatment of HER2-negative metastatic breast cancer (MBC). Eribulin has improved overall survival (OS) in EMBRACE trials. On the other hand, BEV has improved progression free survival (PFS) in several clinical studies, but not revealed prolongation of OS in them. There are difficult situations in making a clinical decision of when to choose which treatment option.Purpose: The purpose of this study is to compare two treatment strategies, Eribulin followed by BEV + PTX versus BEV + PTX followed by Eribulin. We evaluated whether sequential order of treatment affects survival benefit in patients who have been treated with both BEV + PTX and Eribulin in the real world. Methods: All patients who started BEV + PTX and Eribulin treatment for MBC from Aug-2011 to Jun-2018 were selected. Among 264 patients recorded in the TBCRG (14 institutions of Research Group) database, 180 patients had HER2-negative MBC. Of these, 84 patients were treated with both BEV + PTX and Eribulin sequentially regardless of treatment line. To evaluate the influence of sequential order, we compared the efficacy of Eribulin followed by BEV + PTX (arm E-B) to treatment with the reverse sequence (arm B-E). We used the two different analytical approaches to rubstify the findings from this study. Results: 38 patients were treated with E-B and 46 patients with the B-E sequence. We analyzed 60 cases within 3rd-line. In the entire cohort, the median time to failure of strategy (TFS) was 9.9 and 16.8 months in arm E-B and arm B-E, respectively (HR = 0.503, 95%CI 0.298-0.889, p=0.017). The respective median OS was 17.2 and 28.0 months (HR = 0.663, 95%CI 0.349-1.261. p=0.21). Similar HRs were derived from the PSMA and IPTWA cohort in TFS. Using PSMA, TFS was 9.0 and 14.1 months in arm E-B and arm B-E, respectively (HR = 0.406, 95%CI 0.172-0.955, p=0.039). The respective median OS was 12.8 and 24.0 months (HR = 0.61, 95%CI 0.232-1.6, p=0.315). Using IPTWA, TFS was 10.2 and 14.8 months in arm E-B and arm B-E, respectively (HR = 0.621, 95%CI 0.423-0.913, p=0.015). The respective median OS was 17.5 and 24.0 months (HR = 0.86, 95%CI 0.547-1.352, p=0.513).Conclusion: These results suggest that when patients with HER2-negative MBC are treated with both BEV + PTX and Eribulin, patients with prior BEV + PTX treatment is more likely to show more significant difference in results benefit than patients who are treated with prior Eribulin treatment. Citation Format: Koshi Matsui, Mitsuharu Earashi, Takuya Nagata, Akemi Yoshikawa, Wataru Fukushima, Zensei Nozaki, Yasuko Tanada, Kaeko Oyama, Katsuo Shimada, Kaoru Kiyohara, Tetsuro Shimizu, Keiko Iwata, Toru Yoshida, Kiichi Maeda, Akiyoshi Nakakura, Satoshi Morita, Tsutomu Fujii. Effect of Bevacizumab and Eribulin for metastatic breast cancer in the real world evaluated using the propensity score matching analysis (PSMA) and inverse probability of treatment weighting analysis (IPTWA) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-12.

Eribulin monotherapy in heavily pretreated metastatic breast cancer patients in real life.

Our retrospective, single-center study aimed at evaluating the efficacy and safety of eribulin in heavily pretreated metastatic breast cancer (MBC) in routine clinical practice. Twenty-eight patients treated with eribulin for MBC between May 2014 and November 2017 were included in our study. Clinical and biological assessment of toxicity was controlled at each visit. Tumor response was evaluated every three cycles of treatment. Median age at eribulin treatment was 52.5-year. Tumors were hormone receptor positive (71.4%), HER2-positive (10.7%), and triple negative (TN) (25%). Most of the patients (92.8%) presented with visceral metastases, mainly in the lymph nodes (57.1%) and liver (53.6%). Median previous metastatic chemotherapy line was 4 [1-7]. Median number of metastatic sites were 3 (1-4). Median number of eribulin cycles was 4. At the end of follow-up period, 36% of the patients were still alive. Eighteen patients died due to disease progression. The objective response rate was 21.5% with a 42.9% clinical benefit rate. Median progression-free survival and overall survival (OS) were 4 (95% CI: 2.7-5.2) and 14 (95% CI: 11.8-16.1) months, respectively. Treatment was well tolerated. None of the patients discontinued eribulin treatment due to toxicity. The most commonly reported toxicities were asthenia (71.4%), peripheral neuropathy (67.9%), and neutropenia (46.4%). Eribulin is an effective new treatment option in heavily pretreated MBC, with a manageable toxicity profile. Our results confirm that treatment with eribulin is feasible and safe in real-world patients.

Serum microRNA-based prediction of responsiveness to eribulin in metastatic breast cancer.

The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.

The safety of eribulin for the treatment of metastatic breast cancer

ABSTRACTIntroduction: Eribulin mesylate is a highly potent anticancer agent approved for use in pretreated metastatic breast cancer (MBC). Clinical trials of eribulin in MBC have demonstrated activity against this tumor type, and a phase 3 study in patients with MBC previously treated with an anthracycline and a taxane showed a significant increase in overall survival (OS) with eribulin versus control regimens.Areas covered: This review presents overviews of the development of eribulin, its pharmacology, and its efficacy in MBC. A detailed review of its safety profile is presented, and the safety of eribulin is compared with other agents commonly used to treat MBC.Expert opinion: As eribulin is the only drug shown to improve OS in patients with pretreated MBC, it is an important treatment option for many patients. Eribulin is currently considered a second-line (Europe) or third-line (United States) therapy, and studies have been examining use in the first-line setting. The use of eribulin in combination with other therapies is beginning to be explored because its manageable safety profile makes it an ideal combination-treatment partner. Emerging eribulin combination-treatment data suggest a manageable toxicity profile, and eribulin is set to be a key drug for the treatment of MBC in the future.

Perspectives on the mechanism of action and clinical application of eribulin for metastatic breast cancer.

Eribulin is a novel microtubule inhibitor with mitotic and nonmitotic mechanisms of action. Both pooled and subgroup analyses from large-scale Phase III clinical trials demonstrated that eribulin has substantial activity in patients with pretreated (anthracycline and a taxane) advanced or metastatic breast cancer. We review recent pharmacological and clinical findings pertaining to eribulin use in metastatic breast cancer - particularly highlighting eribulin in difficult-to-treat and aggressive disease, and safety data in specific patient populations.Additionally, recent advancements in our understanding of the mechanism of action of eribulin and potential future directions for its clinical development are discussed. Ongoing studies of eribulin in combination with immunotherapies and established cytotoxic agents may help shape the future landscape of breast cancer treatment.

Abstract P1-14-02: A phase 2 study of low dose metronomic eribulin in metastatic breast cancer

Abstract Background: Eribulin mesylate is a non-taxane microtubule dynamics inhibitor approved by FDA in treatment of metastatic breast cancer (MBC) based on improvements in overall survival in the pivotal EMBRACE trial. Eribulin is approved at 1.4mg/m2 administered D1,8 of q21d cycle. However, this dose and schedule may have significant myelosuppression and peripheral neuropathy requiring dose reductions and treatment delays for some patients. We hypothesized that a low dose metronomic schedule will allow responding patients to remain on treatment, resulting in longer TTP (time to progression) and decreased incidence of toxicities and treatment-related discontinuations. Methods: A multi-site prospective open-label phase II trial of metronomic dosing of eribulin in patients with MBC has completed accrual of 60 patients, outcomes will be updated at presentation. Patients whose disease had progressed following 1-6 prior regimens with prior exposure to a taxane, ECOG performance status of 0 – 2, measurable disease per RECIST 1.1, with normal marrow and organ function were eligible. Eribulin was administered at 0.9mg/m2 weekly for 3 out of 4 weeks. For patients with HER2 positive disease, concurrent trastuzumab administration was allowed. Concurrent denosumab or bisphosphonates were allowed for patients with bone disease. Results: 60 patients were enrolled, average age 58 (range 34-83). Majority were postmenopausal Caucasian females, but the study included African American, Hispanic, native American, male patients. The majority of tumors were ER+, infiltrating ductal, but the study included 13 HER2+, and 12 TN tumors, with 5 ILC, and 5 mixed ILC/IDC. Nearly half of the enrolled patients had clinical benefit from the regimen, remaining on therapy for 6 months or longer, with stable disease or response; 50% had progression PD at 3 months 32% had stable disease and 18% had a partial or complete response (1, long term). Overall Survival, OS, for the entire group of heavily pre-treated patients was 1.2 years, with TN and HER2 positive patients faring better than ER+ in this small study. One HER2+ patient remains in long-term remission, off chemotherapy. The regimen was extremely well tolerated. The majority of the patients experienced grade 0 or 1 toxicity for alopecia (48/60) and peripheral neuropathy (7 with grade 2 neuropathy, 5 pre-existing, 2 with grade 3 neuropathy). There were few dose reductions (n=15), thrombocytopenia (11 grade 1 only), or use of G-CSF (14). Conclusions: Metronomic weekly low dose eribulin appears to be an active and tolerable regimen with less myelosuppression, alopecia and peripheral neuropathy than is seen with approved dose, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen. Outcomes will be updated at presentation. Citation Format: Chalasani P, Liu AJ, Khanjian JA, Peha M, Buening BJ, Gadi VK, Specht JM, Salazar L, Linden HM. A phase 2 study of low dose metronomic eribulin in metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-02.

313P - Eribulin in metastatic breast cancer the UK experience: A multi-centre retrospective 577 patient study

313P - Eribulin in metastatic breast cancer the UK experience: A multi-centre retrospective 577 patient study

409 (PB-042) - Benefits in early use of eribulin in metastatic breast cancer: A 7-year UHNM experience

409 (PB-042) - Benefits in early use of eribulin in metastatic breast cancer: A 7-year UHNM experience

P1-013 - Eribulin efficacy for metastatic breast cancer amongst the real-world treatment pattern

Treatments options for metastatic breast cancer (MBC) have become more efficacious and numerous. Eribulin is an active agent for MBC treatment, but the effective usage of this drug is still unclear. Although the usage of eribulin for MBC in Europe is limited to patients who exposed to minimum of two previous chemotherapy regimens including anthracyclines and taxanes in the adjuvant or metastatic setting, there is no such strict limitation in Japan. The purpose of this retrospective study is to evaluate effective usage of erubulin in pretreated metastatic breast cancer patients in daily practice. Chart review was done for the patients who underwent chemotherapy, which include at least paclitaxel or eribulin for metastatic breast cancer between October 2012 and April 2016 in our single institute. One hundred and fifty patients were included in our cohort. The primary efficacy measure assessed overall survival (OS). Among human epidermal growth factor receptor 2 (HER2) negative patients, 51 received eribulin (eribulin group) and 66 received conventional chemotherapy excluding erubulin (non-eribulin group). The median OS from MBC diagnosis in the eribulin group was 39.0 months compared with 22.7 months in the non-eribulin group [hazard ratio (HR): 0.46, 95%CI 0.29-0.73; p = 0.001]. Eribulin seemed to have significant survival benefit in patients with lung metastasis, but not in patients without lung metastasis in our cohort. Same trend was recognized with liver metastasis, or bone metastasis. Eribulin therapy may have a survival benefit in Japanese women with HER2 negative MBC. And may have benefit in MBC patients with lung, liver or bone metastasis.