er-086526 and Liver-Neoplasms

Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician's choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL.. HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m. Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P < 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of -9.4 and -10.8 points, respectively.. There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression.. NCT01492101.

Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Albumins; Anorexia; Antineoplastic Agents; Body Image; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cancer Pain; Deoxycytidine; Docetaxel; Dyspnea; Epothilones; Fatigue; Female; Furans; Gemcitabine; Health Status; Heterocyclic Compounds, 4 or More Rings; Humans; Ketones; Liver Neoplasms; Lung Neoplasms; Middle Aged; Nausea; Paclitaxel; Polyethylene Glycols; Quality of Life; Reproductive Health; Sleep Initiation and Maintenance Disorders; Taxoids; Vinblastine; Vinorelbine; Vomiting

Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC).. In this single-arm, multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m(2) eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review.. Patients (N = 80) had received a median of three prior chemotherapy regimens (range 1-5). ORR was 21.3% [95% confidence interval (CI) 12.9-31.8; all partial responses (PRs)], stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1-38.6). Median duration of response was 3.9 months (95% CI 2.8-4.9), progression-free survival was 3.7 months (95% CI 2.0-4.4) and overall survival was 11.1 months (95% CI 7.9-15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4).. Eribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Furans; Humans; Japan; Ketones; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Taxoids; Treatment Outcome; Tumor Burden

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.

Topics: Acute-On-Chronic Liver Failure; Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Liver Neoplasms; Middle Aged; Treatment Outcome

The 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.. In 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.. Mild 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.

Topics: Antineoplastic Agents; Bilirubin; Breast Neoplasms; Dose-Response Relationship, Drug; Female; Furans; Humans; Ketones; Liver Function Tests; Liver Neoplasms; Practice Guidelines as Topic; Transaminases; Treatment Outcome

Hepatic impairment in breast cancer arises from metastatic spread of tumor cells to the liver and signals a poor prognosis. Systemic therapy is the mainstay of treatment. Three women with hepatic dysfunction secondary to breast cancer who were treated with eribulin are presented herein. In the first case, third-line eribulin at the time of acute liver failure due to metastases maintained response for up to 9 months with good tolerability. In the second case, a woman with secondary bone and liver disease had progression-free survival of 5 months to third-line eribulin and, upon rechallenge after a drug holiday, had almost four more months of stable disease. Last, a heavily pretreated patient with secondary bone and hepatic involvement showed a response to fourth-line eribulin.

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Liver Neoplasms; Middle Aged

We report the case of a 50-year-old woman with a triple-negative Ki67 80% breast cancer with liver metastases, who obtained a radiological long-lasting complete response after treatment with eribulin. The patient initially experienced progressive disease after a standard anthracycline/taxane-based adjuvant chemotherapy, a first-line treatment for metastatic disease with paclitaxel-bevacizumab, and a second-line maintenance treatment with bevacizumab and capecitabine. Eribulin was administered according to a 1.23 mg/m2 scheme on days 1 and 8 every 3 weeks, and the treatment was always well tolerated. After 45 cycles of therapy, we still detected radiological evidence of complete response on liver sites of disease. This case report underlines the great efficacy of eribulin as third-line treatment for metastatic disease in a very aggressive form of breast cancer.

Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Female; Furans; Humans; Ketones; Liver; Liver Neoplasms; Middle Aged; Triple Negative Breast Neoplasms

Liver metastases are very common in metastatic breast cancer (MBC); current treatments for these lesions are based on systemic chemotherapy, endocrine- or human epidermal growth factor receptor 2 (HER2)-targeted therapy, and palliative therapy. However, no standard approach has been clearly identified for second and further chemotherapy lines in MBC patients. In the phase III clinical trial EMBRACE, eribulin was particularly effective in reducing liver lesions and improving both overall survival and progression-free survival in liver MBC patients. In this series, we collected 8 case reports of Italian clinical practice in which eribulin has shown significant efficacy in reducing liver metastases in MBC patients: complete response was reported in 2 patients, and 4 patients achieved partial response. The treatment was well tolerated, thus confirming that eribulin is a suitable therapeutic option for elderly patients and for those who have metastatic HER2-negative disease. In the setting of MBC, the sequencing of therapeutic agents should consider expected response, side effects, tumor characteristics, and patient's preferences, in order to successfully tailor the most appropriate therapy beyond earlier lines.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Liver; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2

A middle-aged woman with a history of leiomyosarcoma of the uterus treated with surgery and adjuvant chemotherapy suffered a bulky metastatic recurrence 1 year later. She elected treatment with palliative eribulin, presenting with acute renal failure and electrolyte abnormalities consistent with tumour lysis syndrome on cycle 1 day 8. Despite aggressive supportive care and treatment including intravenous hydration, bicarbonate and rasburicase, she continued to decline, ultimately foregoing haemodialysis in favour of palliative care and passed away in the hospital.

Topics: Acute Kidney Injury; Antimitotic Agents; Fatal Outcome; Female; Furans; Humans; Ketones; Leiomyosarcoma; Liver Neoplasms; Middle Aged; Tumor Lysis Syndrome; Uterine Neoplasms

The 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.. We 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.. Of 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.. The 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.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Furans; Humans; Kaplan-Meier Estimate; Ketones; Liver Neoplasms; Middle Aged; Patient Selection; Retrospective Studies; Treatment Outcome

There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven. A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model.. We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs.. Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Drug Costs; Female; France; Furans; Humans; Ketones; Linear Models; Liver Neoplasms; Lung Neoplasms; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Prognosis; Proportional Hazards Models; Retrospective Studies; Skin Neoplasms; Survival Rate

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Female; Furans; Humans; Ketones; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Retrospective Studies

Eribulin mesylate is approved for the treatment of metastatic breast cancer (MBC) patients after progression with anthracyclines and taxanes. Eribulin appears especially promising when combined with trastuzumab, according to the results of a recent Phase II trial in first-line setting. Here we report the case of a young, pretreated, HER2(-) MBC patient, who achieved a long-term clinical benefit with eribulin alone and in combination with trastuzumab after re-biopsy on liver metastases showed HER2 amplification. Although it is unique for its evolving clinical/biomolecular picture, this case adds anecdotal evidence to the efficacy and tolerability of this combination. However, Phase III trials are warranted to confirm its potential in first and subsequent lines of MBC treatment.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Furans; Humans; Ketones; Liver Neoplasms; Lung Neoplasms; Retreatment; Tomography, X-Ray Computed; Trastuzumab; Treatment Outcome

Case 1: Case 1 involved a 42-year-old woman who had been diagnosed as having advanced breast cancer (Stage III B). She had previously received 6 courses of cyclophosphamide, epirubicin, and 5-fluorouracil CEF, 14 courses of weekly paclitaxel, and 2 courses of vinorelbine( VNR). After the courses of chemotherapy, she underwent modified radical mastectomy with axillary lymph node dissection. Two years after surgery, lung metastases were found, and the patient received 6 courses of weekly paclitaxel and 13 courses of nab-paclitaxel. However, the lung metastases progressed after the courses of chemotherapy, and therefore, we decided to administer eribulin as third-line chemotherapy. Eribulin was effective against the lung metastases for more than 1 year. Case 2: Case 2 involved a 52-year-old woman who had been diagnosed as having Stage IIB breast cancer. She had received 4 courses of CEF and 4 courses of docetaxel as neo-adjuvant chemotherapy. After chemotherapy, she underwent breast-conserving surgery with axillary lymph node dissection. Five years postoperatively, multiple liver metastases were found, and the patient received 3 courses. However, the liver metastases progressed after this chemotherapy. Subsequently, we administered nab-paclitaxel; however, it produced severe side effects. We then decided to administer eribulin as second-line chemotherapy. Eribulin was effective against the liver metastases for more than 1 year.

Topics: Adult; Breast Neoplasms; Female; Furans; Humans; Ketones; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Staging; Time Factors