Safety Of Eribulin Research Articles

608TiP - BRAVERY study: A multicenter phase II study of eribulin in patients with BRAF V600E mutant metastatic colorectal cancer (EPOC1701)

Background: BRAF V600E mutations are present in 5-10% of metastatic colorectal cancer (mCRC) patients, associated with aggressive biology and limited response to standard chemotherapy, especially in second line and beyond. BRAF V600E mutant CRCs have different patterns of gene expression from the BRAF wild-type, and preclinical evidence suggests that microtubule inhibitors have a potential antitumor effect on xenograft models of BRAF V600E mutant CRC; among them, eribulin has greater growth inhibitory activity than either vinblastine or paclitaxel in vitro. In addition, we have experienced a hint of activity for BRAF V600E mutant CRC patients with tumor shrinkage following eribulin treatment (Masuishi T, et al. Ann Oncol, 2018). Trial design: BRAVERY study is a multicenter phase II study to evaluate the efficacy and safety of eribulin in patients with BRAF V600E mutant mCRC detected in either tumor tissue (primary analysis cohort) or circulating tumor DNA (ctDNA) assay (liquid biopsy cohort). Key eligibility criteria are refractory or intolerant to at least one regimen (including irinotecan or oxaliplatin) containing fluoropyrimidine, an age of 20 years or older, and ECOG performance status of 0–1. Eribulin is administered intravenously at a dose of 1.4 mg/m2 on Days 1 and 8, repeated every 21 days. Primary endpoint is confirmed objective response rate (ORR) by investigator’s assessment. A sample size of the primary analysis cohort is calculated 27 using two-stage design with ORR of 25% deemed promising and 5% unacceptable (one-sided α, 0.05; β, 0.1). Secondary endpoints include progression-free survival, time to treatment failure, disease control rate, overall survival and adverse events. Furthermore, pretreated tissue and serial blood samples are collected for biomarker analysis; especially focused on gene expression associated with BRAF mutant-like CRC as a predictive marker, BRAF mutant allele frequency in ctDNA as early detection of efficacy, and acquired gene alteration as resistant mechanism to eribulin. At the end of April 2018, four patients have been enrolled in primary analysis cohort since March 2018. Clinical trial information: UMIN000031221 and 000031552. Clinical trial identification: UMIN000031221 and 000031552. 26/March/2018. Legal entity responsible for the study: Hiroya Taniguchi. Funding: Japan Agency for Medical Research and Development. Disclosure: T. Esaki: Grant and personal fees: Eisai. All other authors have declared no conflicts of interest.

Eribulin in Heavily Pretreated Metastatic Breast Cancer Patients in the Real World: A Retrospective Study

Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m² on days 1 and 8 every 21 days. Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.

Predictive Factors of Eribulin Activity in Metastatic Breast Cancer Patients

Objectives: Predictive factors of response to eribulin are lacking. We aimed to investigate the activity and safety of eribulin in a real-world population of metastatic breast cancer (MBC) patients and to identify possible predictive factors of progression-free survival (PFS) and objective response. Methods: We retrospectively analyzed 71 eribulin-treated MBC patients. Best response rate, PFS, and adverse events (AEs) were evaluated. The impact of different clinical-pathological factors on PFS was evaluated using the Cox proportional hazards model. Predictive factors of response were identified by discriminant function analysis (DFA). Results: Median PFS was 3.75 months (95% CI, 2.39–4.48); 12 patients (16.90%) achieved partial response (PR), 27 (38.03%) stable disease. The most common AEs were fatigue (25.83%), neutropenia (16.56%), and peripheral neuropathy (13.91%). A worse performance status (p = 0.025) and a higher number of metastatic organ sites (p = 0.011) were associated with a worse PFS under eribulin. Overall, in the DFA-predictive model, neutrophil-to-lymphocyte ratio at baseline, estrogen receptor, Ki67, histology, and age were predictive of PR with 100% accuracy. Conclusions: Activity and safety profiles of eribulin were consistent with literature data. Performance status and number of metastatic sites were predictive factors of PFS. DFA could be a promising tool to discriminate responses to eribulin among MBC patients.

Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: a multicenter, single-arm trial

BackgroundEribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer.MethodsThe primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated.ResultsBetween December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5–61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0–73.5) and 78.1% (95% CI 63.8–92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1–9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable.ConclusionsEribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer.Trial registrationsThis trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334).Date of trial registration: April 1st, 2013.

341 (PB-136) - Efficacy and safety of Eribulin in patients with metastatic breast cancer in routine practice of St. Petersburg clinical oncological dispensary

341 (PB-136) - Efficacy and safety of Eribulin in patients with metastatic breast cancer in routine practice of St. Petersburg clinical oncological dispensary

Efficacy and safety of eribulin in patients with locally advanced or metastatic breast cancer not meeting trial eligibility criteria: a retrospective study

BackgroundThe efficacy and safety of eribulin in patients with locally advanced or metastatic breast cancer has been demonstrated in phase III trials. However, as patients receiving eribulin in daily practice do not necessarily meet all the eligibility criteria of clinical trials, data for such patients are limited.MethodsWe identified patients with locally advanced or metastatic breast cancer, treated with eribulin monotherapy between July 2011 and December 2015 at the National Cancer Center Hospital, Tokyo, Japan. Patients who would have met the following eligibility criteria from the EMBRACE trial were included in the eligible group, and the rest were included in the ineligible group: 1) Eastern Cooperative Oncology Group Performance status 0–2; 2) adequate function of principal organs; and 3) absence of active infection. We compared the relative dose intensity (RDI), tumor response, progression-free survival (PFS), overall survival (OS), and adverse events between the groups. Nominal and continuous values were compared using the Fisher’s exact test and Mann-Whitney U test, respectively. Survival outcomes were determined using Kaplan-Meier estimation, and between-group differences were assessed using the log-rank test.ResultsOf the 203 patients included, 34 were classified into the ineligible group and 169 into the eligible group. Initial dose reduction and treatment discontinuation due to adverse events (AEs) were more common in the ineligible group (initial dose reduction: 23.5% in the ineligible group vs. 7.7% in the eligible group, p = 0.011; treatment discontinuation due to AEs: 11.8% vs. 3.0%, p = 0.045). However, RDI (66% vs. 71%, p = 0.130), response rate (15.6% vs. 18.1%, p = 1.000), PFS (3.7 months vs. 4.0 months, p = 0.913), OS (11.5 months vs. 16.1 months, p = 0.743), AEs requiring hospitalization (5.9% vs. 6.5%, p = 1.000), and grade 3/4 AEs were similar in both groups. PFS, OS, AEs requiring hospitalization, and discontinuation due to AEs in the eligible group were comparable to those found in previous phase III trials.ConclusionThe safety and efficacy of eribulin monotherapy was demonstrated in a broader patient population than that eligible for clinical trials. Eribulin may be a treatment option in these patients with locally advanced or metastatic breast cancer, considering dose reduction and pre-existing dysfunctions.

PR99 - Efficacy and Safety of Eribulin in Patients with Triple Negative Metastatic Breast Cancer: Real Life Experience

PR99 - Efficacy and Safety of Eribulin in Patients with Triple Negative Metastatic Breast Cancer: Real Life Experience

PO90 - Efficacy and Safety of Eribulin in Combination with Trastuzimab in HER2-Positive Metastatic Breast Cancer Patients: Real Life Experience

PO90 - Efficacy and Safety of Eribulin in Combination with Trastuzimab in HER2-Positive Metastatic Breast Cancer Patients: Real Life Experience

PR89 - Efficacy and Safety of Eribulin in Patients with HER2-Negative Metastatic Breast Cancer: Real Life Experience

PR89 - Efficacy and Safety of Eribulin in Patients with HER2-Negative Metastatic Breast Cancer: Real Life Experience

Efficacy and safety of eribulin in patients with triple negative metastatic breast cancer: Real life experience.

e12580 Background: Eribulin demonstrates improved overall survival compared to standard treatments, Her2-negative and TNBC patients have the most survival benefit. We sought to describe treatment patterns of eribulin and clinical outcomes among TNBC patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between January 1, 2014 and January 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records (electronic or paper-based) and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 52 TNBC patients were considered by 10 providers. A median of age at start of eribulin was 47,5 (39-55) yrs and ECOG status 0-1 were assessed. Most of the pts (92,3%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of BC treatment to 14 (26,9%) pts, 3rd line – to 9 (17,3%), the 4thand later lines – to 29 (55,8%) pts. Objective response occurred in 5 (9,6%) pts. Stable disease registered in 24 (46,1%) pts. Median PFS was 3,0 months (95% CI 1,9-8,55). Overall the drug was well tolerated. The most common type of toxicity was hematologic. Neutropenia gr II was observed in 8 (15,4) pts and III-IV gr in 6 (11,5%), two cases of febrile neutropenia were registered. 4 (7,7%) pts experienced fatigue gr II. Peripheral neuropathy gr II was observed in 4 (7,7%) pts. Dose reduction due to toxicity was performed in 8 (15,4%) pts. Treatment was never withdrawn due to toxicity. Conclusions: This is the first real-life study of clinical outcomes, for patients initiating eribulin therapy for TNBC in community oncology practices throughout the Russian Federation. . Our experience with Eribulin in TNBC patients confirms it efficacy and safety in all lines of treatment, including intensively pretreated patients in this hard-to-treat population.

Efficacy and safety of eribulin in patients with metastatic breast cancer at early and late application: Real-life experience.

e12579 Background: We sought to describe treatment patterns of eribulin and clinical outcomes associated with early and late use among anthracycline and taxane-pretreated patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between Jan1, 2014 and Jan 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 113 MBC patients were considered by 16 providers. A median age was 53 (44-58) yrs and ECOG status 0-1 were assessed. 57 (50,5%) pts were ER/PR-positive, 37 (32,7%) – triple-negative, 19 (16,8%) – HER2-positive (in combination with trastuzumab). Most of the pts (96,5%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of MBC treatment to 36 (32%) pts (early application), the 3rd and later lines (late application) – to 77 (68%) pts. Clinical response rate (ORR and SD ≥ 6 months) was 44% among early line treated patients (first and second-line combined) and 38% among late line eribulin treated patients. Median PFS was 4,89 months (95% CI 2,84-8,00) among early users and 3,96 months (95% CI 2,04-7,99) among later users. The effectiveness in early eribulin application group was higher, but difference was not statistically significant. Tolerability of the drug was good: withdrawn due to toxicity had 3,5%, dose reduction – 13, 3% of pts. The most common type of toxicity was hematological with neutropenia Gr II in 12 (10,6%) of pts and Gr III – in 8 (7,1%) of pts and 2 pts had febrile neutropenia. 6 (5,3%) pts experienced fatigue Gr II. Peripheral neuropathy Gr II was observed in 8 (7,1%) of pts. Conclusions: This is the first real-life description of clinical outcomes, for patients initiating eribulin therapy for MBC throughout the Russian Federation. Our experience with Eribulin in MBC patients confirms it efficacy and safety in early lines of treatment and intensively pretreated patients.

Phase II study of eribulin with trasutuzumab for pretreated locally advanced or metastatic HER2-positive breast cancer.

e12505 Background: Eribulin mesylate demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received 2 or more chemotherapy regimens. There are limited studies reported about the efficacy of eribulin with trastuzumab as first-line therapy for locally advanced or metastatic HER2-positive breast cancer. The aim of this study was to assess the efficacy and safety of eribulin with trastuzumab as late-line therapy for locally advanced or metastatic HER2-positive breast cancer. Methods: In this multicenter, phase II, single-arm study, patients with locally advanced or metastatic HER2 positive breast cancer who previously received at least one chemotherapeutic regimen, received eribulin at 1.4 mg/m2 intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. The primary end point was ORR, and secondary end points included PFS and safety. Results: Thirty-six patients (median age: 60.5 years) were enrolled. The median number of prior treatment regimens was 4 (range, 1‐8). Twenty-two patients (61.1%) had received prior pertuzumab treatment, 10 patients (27.8%) had prior T-DM1. Patients received a median of 6 cycles of eribulin with trastuzumab (2-13 cycles). The ORR was 17% (CR 0, PR 6) with median PFS of 4.6 months (3.3-7.0 months). The clinical benefit rate was 33%. The most common Grade 3/4 treatment-emergent adverse events were neutropenia in 22 (61%) patients, peripheral neuropathy in 3 (8%; all Grade 3) patients, fatigue in 1 (3%) patients. Five (13.9%) patients had asymptomatic LVEF decline. However, no grade 3 LVEF decline or symptomatic congestive heart failure was observed. The reasons for treatment discontinuation were disease progression in 27 (75%) patients and adverse events in 8 (22%) patients. Conclusions: Eribulin with trastuzumab is an acceptable option in late-line treatment for locally advanced or metastatic HER2-positive breast cancer. Clinical trial information: 000012350.

Eribulin efficacy based on type of metastatic site: a real-life study in heavily pretreated metastatic breast cancer.

The halichondrin B analog, eribulin, exerts an anticancer effect, as reported by several clinical and real-life studies on metastatic breast cancer patients. Here, we evaluated efficacy and safety of eribulin, focusing on response to treatment per metastasis type. This monocentric, real-life study was conducted on 31 heavily pretreated patients with metastatic breast cancer. The median progression-free survival and overall survival were 2.0 and 5.5 months, respectively. All patients (12.9%) responding to eribulin were treated in fourth-line setting. Considering response per metastasis type, bone lesions (13.6%) responded more frequently than other metastases to eribulin. Eribulin exhibited a good overall response rate, with the highest response observed for bone metastases.

Efficacy and safety of eribulin in taxane-refractory patients in the 'real world'.

Recent clinical, randomized and observational studies showed that eribulin, an analogous of Halichondrin B, was beneficial and well-tolerated in heavily pretreated metastatic breast cancer patients. Here, we aim to evaluate the effectiveness and safety of eribulin in taxane-refractory metastatic breast cancer patients. In this subanalysis of the ESEMPIO study database, we selected 91 subjects with well-defined taxane refractoriness and complete data available. 41 patients (45.2%) showed clinical benefit; one complete response (2.2%) and 16 partial responses (17.6%) were observed. Median progression-free survival and median overall survival were 3.1 and 11.6 months, respectively. The most experienced adverse event was asthenia/fatigue (58%), followed by neutropenia (30%). The treatment-related toxicity led to eribulin-dose reduction in 19 patients and suspension in nine. This study shows that eribulin is effective and well tolerated also in taxane-refractory patients in clinical practice.

Efficacy and safety of eribulin as first- to third-line treatment in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

ObjectivesDespite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC. Materials and methodsIn this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated. ResultsOf 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment. ConclusionEribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).

Efficacy and safety of eribulin in various subtypes of breast cancer: data from real clinical practice in Russia

The article presents a pooled experience of the use of eribulin in the real clinical practice of treatment of metastatic breast cancer in Russian oncological institutions. The effectiveness of the drug in monotherapy with HER2‑negative breast cancer was analyzed, groups of patients with most effective use of eribulin were identified depending on the localization of metastases, the most effective lines of therapy. The effectiveness of the drug in combination with trastuzumab in HER2‑positive breast cancer is described, as well as toxic reactions.

F39 - Safety of Eribulin plus Trastuzumab in pre-treated HER2-positive advanced breast cancer (ABC) patients: results from an Italian observational study

F39 - Safety of Eribulin plus Trastuzumab in pre-treated HER2-positive advanced breast cancer (ABC) patients: results from an Italian observational study

Phase 2 study of eribulin mesylate in combination with carboplatin in patients with advanced triple-negative breast cancer.

e12551Background: Treatment of triple negative breast cancer (TNBC) remains one of the most challenging subtypes to treat because of the lack of specific therapies. In addition to the evaluation of platinum in the preoperative setting, studies in the metastatic setting further support that platinum may be active in metastatic TNBC. Another novel mitotic inhibitor currently being studied in this setting is eribulin.The aim of this Phase 2 study was to assess efficacy and safety of eribulin in combination with carboplatin as first-line therapy for locally recurrent or metastatic TNBC. Methods: Eligible patients were females with TNBC who had received one previous chemotherapy regimen in adjuvant setting (including an anthracycline and a taxane, but excluding platinum agents), an ECOG (PS) ≤ 1, and adequate hematological, renal and hepatic function. Patients received eribulin at 1.4 mg/m2 (IV over 2-5 minutes) on days 1 and 8 followed by carboplatin AUC5 (IV over 30 minutes) on day 1 every 21 days until dise...

Eribulin mesylate in advanced breast cancer: retrospective review of a single institute experience.

EMA licensed eribulin mesylate in 2011 for women with advanced breast cancer already treated with at least two lines of chemotherapy, including anthracyclines and taxanes. Azienda Sanitaria Firenze experience is reported to assess the efficacy and safety of eribulin in the real-life setting. Eribulin was infused as per indication. All women treated in the last 2 years were reviewed. A total of 27 women received eribulin. All but one was pretreated with anthracyclines, 97% with taxanes and 87% with capecitabine. Median age was 63 years (range: 27-80). A median of four cycles of eribulin were infused (range: 2-10). Overall response rate was 30% with a 45% of clinical benefit (response plus stable disease for at least 24 weeks). Toxicities have been as expected. Severe toxicities were rare, with one patient experiencing sepsis and 18% developing grade 3 asthenia. Eribulin maintains its activity out of clinical trials, without unexpected toxicities.

Safety of eribulin in Korean patients with metastatic breast cancer.

e12031 Background: EMBRACE/Study305 demonstrated the efficacy of eribulin for the treatment of advanced breast cancer after two-to-five lines of chemotherapy. Only 1% of patients were from Asia Pac...