The safety of eribulin for the treatment of metastatic breast cancer

Peréz-García, José Manuel; Cortés, Javier

doi:10.1080/14740338.2019.1608946

Cited by 17 publications

(16 citation statements)

References 68 publications

(97 reference statements)

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“…Safety profile is an important issue in the treatment of advanced STS. Toxicity data observed in our six patients were consistent with the manageable eribulin toxicity profile reported in previous studies, both in STS and MBC [8,11,12]. In particular, we used a full dose of eribulin in three elderly patients (≥65 years old), reporting no additional adverse event (cases 4, 5 and 6).…”

Section: Discussionsupporting

confidence: 88%

Experience with Eribulin in Pretreated Patients with Advanced Liposarcoma: A Case Series

et al. 2019

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Systemic treatments for advanced soft tissue sarcoma are limited. Eribulin showed activity in metastatic soft tissue sarcoma, particularly liposarcomas. Data from six patients with advanced liposarcoma that received eribulin as third- or fourth-line therapy are presented herein. Eribulin treatment was well tolerated; no grade 3–4 toxicity or therapy delay was observed. Two patients had a partial response; four had a prolonged stable disease. The first case, with pre-existing chronic renal dysfunction, achieved a 6-month stable disease with dose-reduced eribulin. The second case became resectable after eribulin treatment, with a 6-month complete surgical remission. The third case obtained a 7-month stable disease with eribulin and stereotactic body radiotherapy. The last three cases were ≥65 years old, and two of them had objective response with eribulin.

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Section: Discussionsupporting

confidence: 88%

Experience with Eribulin in Pretreated Patients with Advanced Liposarcoma: A Case Series

et al. 2019

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“…It will therefore be interesting to evaluate the power of this marker to predict responsiveness of MBC patients to PARP inhibitor and other DNA repair-related drug treatments in future studies. Eribulin has become a promising drug for MBC, as it mediates improved OS in patients with pretreated MBC [41]. Predictive markers are needed for Eribulin treatment responses, but there are none available.…”

Section: Discussionmentioning

confidence: 99%

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

Schochter

Werner

Köstler

et al. 2020

Cancers

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Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible "biopsy material" to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2-CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan-Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC.Cancers 2020, 12, 930 2 of 18 13.3 months after diagnosis of metastatic sites, TNBC has a particularly poor prognosis. Often patients develop a resistance to first-line chemotherapy very rapidly, resulting in a median duration of first-line palliative chemotherapy of 11.9 weeks [1].Triple-negative tumors are characterized by the lack of HR and HER2 expression, but aside from this common feature this subgroup includes very heterogeneous tumors. A mutation in BRCA1 or 2 is found in up to 20% of triple-negative metastatic patients [2]. The proteins encoded by BRCA genes are critically involved in DNA double-strand break (DSB) repair, more specifically, in the error-free pathway of homologous recombination repair (HRR) [3]. In TNBC, a high prevalence of gene mutations as well as epigenetic changes result in BRCAness, compromising safe DNA repair through HRR [2,4,5]. The DNA damage response factor 53BP1 is crucial in protecting DNA ends in BRCA1-defective cells from resection and entry into error-prone repair pathways [6][7][8]. It has been demonstrated that 53BP1 expression in breast cancer is associated with poor prognosis, particularly in TNBC frequently showing BRCA1 dysfunction [7,9].Due to the lack of predictive targets, chemotherapy was the only treatment option available for a long time. This results in an urgent clinical need for new therapies. During the last years, new drugs such as the Poly(ADP-ribose) polymerase (PARP)-inhibitors targeting HRR-defective tumors were studied in several clinical trials. Two different phase III trials (OlympiaAD and EMBRACA) showed an impro...

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“…Published real-world data and additional clinical trials for eribulin show similar results of AE's: neutropenia (47-54%), asthenia (15-54%), peripheral neuropathy (24-35%) [5][6][7][8]. In addition to supportive care, neutropenia and peripheral neuropathy are generally managed by dose delays or dose reductions, which occur in a significant proportion of patients (30-50%) [4,9].…”

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confidence: 71%

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

Chalasani

Farr

et al. 2021

Breast Cancer Res Treat

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Background Treatment 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. Methods We 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. Findings We 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. Interpretation Metronomic 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.

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The safety of eribulin for the treatment of metastatic breast cancer

Cited by 17 publications

References 68 publications

Experience with Eribulin in Pretreated Patients with Advanced Liposarcoma: A Case Series

Experience with Eribulin in Pretreated Patients with Advanced Liposarcoma: A Case Series

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

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

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