Factors predictive of second-line chemotherapy in soft tissue sarcoma: An analysis of the National Genomic Profiling Database.

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The indications for these drugs in STS other than L-sarcoma have not been established. Here we explored the prognosis, mutation profiles, and drug-response factors in STS using real-world big data. Clinicogenomic data on 1761 patients with sarcoma who underwent FoundationOne CDx were obtained from a national database in Japan. Patients with TP53 and KDM2D mutations had a significantly shorter survival period of 253 (95% CI, 99-404) and 330 (95% CI, 20-552) days, respectively, than those without mutations. Non-supervised clustering based on mutation profiles generated 13 tumor clusters. The response rate (RR) to trabectedin was highest in an MDM2-amplification cluster (odds ratio [OR]: 2.2; p = 0.2). The RR was lowest for eribulin in an MDM2-amplification cluster (OR: 0.4; p = 0.03) and highest in a TERT-mutation cluster (OR: 3.0; p = 0.03). The RR was highest for pazopanib in a PIK3CA/PTEN-wild type cluster (OR: 2.1; p = 0.03). In particular, patients harboring mutations in genes regulating the PI3K/Akt/mTOR pathway had a lower RR than patients without mutations (OR: 0.3; p = 0.04). In STS, mutation profiles were more useful in predicting the drug response than histology. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second-line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.

Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2-negative metastatic breast cancer.

BACKGROUND: Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863). METHODS: We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise. FINDINGS: Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months). INTERPRETATION: Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.

Real-world treatment patterns and clinical outcomes in patients treated with eribulin after prior phosphoinositide 3-Kinase inhibitor treatment for metastatic breast cancer.

PURPOSE: In 2010, the US Food and Drug Administration approved eribulin for the treatment of metastatic breast cancer (MBC). Since then, the treatment landscape has evolved with many new therapy classes, a more recent one being the small molecule inhibitors of phosphoinositide 3 kinase (PI3K). We sought to characterize the treatment patterns and clinical outcomes of patients with MBC who received eribulin following prior treatment with a PI3K inhibitor. METHODS: A retrospective cohort study based on medical record review included MBC patients who initiated eribulin between March 2019 and September 2020 following prior treatment with a PI3K inhibitor was conducted. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated from the initiation of eribulin therapy using Kaplan-Meier analyses. RESULTS: 82 eligible patients were included. Patients' median age at eribulin initiation was 62 years; 86.5% had hormone receptor-positive, human epidermal growth factor receptor 2-negative tumors. Eribulin was most often administered in the second or third line (82.9%) in the metastatic setting. Best overall response on eribulin was reported as complete or partial response in 72% of the patients. The median rwPFS was 18.9 months (95% confidence interval [CI], 12.4-not estimable); median OS was not reached. The estimated rwPFS and OS rates at 12 months were 63.3% (95% CI, 50.5-73.7) and 82.6% (95% CI, 72.4-89.3), respectively. CONCLUSION: Our real-world study suggests that eribulin may be a potential treatment option for MBC patients who fail a prior PI3K inhibitor.

Eribulin for patients with metastatic extramammary Paget disease: Study protocol for a single-arm phase II trial.

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that predominantly affects the anogenital areas of the elderly. Although the efficacy of docetaxel and other cytotoxic agents for advanced EMPD has been reported in small retrospective case studies, no treatment has been proven effective in prospective clinical trials. We established the world's first in vivo EMPD experimental model (a patient-derived xenograft model). In our treatment experiment, xenograft tumours showed a remarkable response to eribulin. This study evaluates the efficacy of eribulin for patients with advanced EMPD. In October 2022, we started a single-arm phase II trial to evaluate the efficacy of eribulin as a treatment for adult patients with unresectable EMPD with measurable lesions. Enrolment in this clinical trial is open to patients with any prior treatment for EMPD. The primary endpoint is overall response rate; the secondary endpoints include disease control rate, overall survival, progression-free survival and adverse events. The study protocol was approved by the Ethics Committee of Hokkaido University and the other collaborating institutions. If the primary endpoint is met, it is our hope that eribulin will be regarded as a standard medication for patients with advanced EMPD.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin.

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

Natural-source payloads used in the conjugated drugs architecture for cancer therapy: Recent advances and future directions.

Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.

Cost-benefit evaluation of advanced therapy lines in metastatic triple-negative breast cancer in Germany.

BACKGROUND: Triple-negative breast cancer (TNBC) is responsible for 10-20% cases of breast cancer and is resulting in rising healthcare costs. Thus, health-economic evaluations are needed to relate clinical outcomes and costs of treatment options and to provide recommendations of action from a health-economic perspective. METHODS: We investigated the cost-benefit-ratio of approved treatment options in metastatic TNBC in Germany by applying the efficiency frontier approach. These included sacituzumab-govitecan (SG), eribulin, vinorelbine, and capecitabine. Clinical benefit was measured as (i) median overall survival (mOS) and (ii) health-related quality of life (HRQoL) in terms of time to symptom worsening (TSW). To assess medical benefits, literature was systematically reviewed in PubMed for (i) and (ii), respectively. Treatment costs were calculated considering annual direct outpatient treatment costs from a statutory healthcare payer perspective. It was intended that both, (i) and (ii), yield an efficiency frontier. RESULTS: Annual direct outpatient treatment costs amounted to EUR 176,415.21 (SG), EUR 47,414.14 (eribulin), EUR 13,711.35 (vinorelbine), and EUR 3,718.84 (capecitabine). Systematic literature review of (i) and statistical analysis resulted in OS values of 14.3, 9.56, 9.44, and 7.46 months, respectively. Capecitabine, vinorelbine, and SG are part of the efficiency frontier including OS. The highest additional benefit per additional cost was determined for vinorelbine, followed by SG. Systematic review of (ii) revealed that no TSW data of TNBC patients receiving vinorelbine were available, preventing the presentation of an efficiency frontier including HRQoL. CONCLUSIONS: Vinorelbine is most cost-effective, followed by SG. Health-economic evaluations support decision-makers to assess treatment options within one indication area. In Germany, the efficiency frontier can provide decision support for the pricing of innovative interventions. Results of our analysis may thus guide reimbursement determination.

The effects of the combination of temozolomide and Eribulin on T98G human glioblastoma cell line: an ultrastructural study.

Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours.

Comprehensive prognostic prediction of metastatic breast cancer treated with eribulin using blood­based parameters and ratio.

Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. In the present study, the relative effects of NLR and PLR on survival in patients with metastatic BC were quantified and their clinical prognostic value was evaluated. This retrospective study included 156 patients with metastatic BC who received eribulin monotherapy at Saitama Medical University International Medical Center. Clinicopathological features were examined (peripheral blood findings and biochemical liver and kidney function test results) and univariate and multivariate analyses were conducted of the overall survival (OS). The 156 patients treated with eribulin had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) >1,500/µl, NLR <3.0, and PLR <150 had significantly longer OS than those with lower ALC, and higher NLR and PLR (median OS, 25.5 vs. 15.5 months; P<0.01; 20.3 vs. 13.6 months, P<0.01; and 29.2 vs. 14.8 months; P<0.001, respectively). Patients with anemia [hemoglobin (Hb) <10 g/dl] or liver dysfunction [albumin-bilirubin (ALBI) grade 2/3] had significantly shorter OS than those without (P<0.001, respectively). Multivariate analysis revealed low ALBI grade (P<0.001), high Hb (P<0.01) and low PLR (P<0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia and liver dysfunction might be factors associated with prolonged OS in patients with metastatic BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing.

Eribulin in breast cancer: Current insights and therapeutic perspectives.

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.

Prognostic Factors for Long-Term Eribulin Response in a Cohort of Patients With HER2-Negative Metastatic Breast Cancer.

CONTEXT AND AIMS: Eribulin is used in taxane and anthracycline refractory HER2-negative metastatic breast cancers (MBC). Patients treated in pivotal clinical trials achieved low survival rates, therefore, the identification of prognostic criteria for long progression-free survival (PFS) is still an unmet medical need. In this study, we sought to determine potential prognostic criteria for long-term eribulin response in HER2-negative MBC. METHODS: Our retrospective cohort includes female patients with HER2-negative MBC treated with eribulin in Franche-Comté, France. We defined a long-term response as at least 6 months of eribulin treatment. The primary endpoint was the analysis of criteria that differ according to the progression-free survival. Secondary outcomes concerned overall survival and response rate. RESULTS: From January 2011 to April 2020, 431 patients treated with eribulin were screened. Of them, 374 patients were included. Median PFS was 3.2 months (2.8-3.7). Eighty-eight patients (23.5%) had a long-term response to eribulin. Four discriminant criteria allowed to separate PFS in 2 arms (PFS < 3 months or > 6 months) with a 78% positive predictive value: histological grade, absence of meningeal metastasis, response to prior chemotherapy, and OMS status. We have developed a nomogram combining these 4 criteria. Median overall survival was 8.5 months (7.0-9.5). CONCLUSION: Eribulin response in MBC can be driven by clinical and biological factors. Application of our nomogram could assist in the prescription of eribulin.

Efficacy and safety of eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with anthracycline/taxanes.

BACKGROUND: This prospective real-world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. PATIENTS AND METHODS: In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo-/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. RESULTS: One hundred and thirty-four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3-15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first- or second-line treatment was significantly better than those who received eribulin as ≥3-line treatment (6.9 months [95% CI: 3.2-8.8] vs. 4.0 months [95% CI: 3.4-4.6], p = 0.006). The mPFS of patients with triple-negative, HER2-positive, and HER2(-)/HR(+) was 3.4 (95% CI: 2.7-4.1), 6.2 (95% CI: 2.3-10.1) and 5.0 months (95% CI: 4.1-5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6-6.3] vs. 4.0 months [95% CI: 3.3-4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non-TNBC receiving eribulin as ≤2-line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment-related adverse events. CONCLUSION: Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real-world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Chemotherapy With Eribulin Following Potentially Curative Surgery in Patients With Localized Liposarcoma.

BACKGROUND/AIM: Soft tissue sarcomas are rare and heterogenous malignancies with high recurrence rates following resection and a poor prognosis in advanced stages. Eribulin is used in metastatic soft tissue sarcoma patients, who have failed first line chemotherapy and has been approved for patients with pretreated advanced liposarcoma (LPS) in the United States and Europe following the publication of data of a phase III trial. In addition, no data are available for eribulin as postoperative treatment after potentially curative surgery. We, thus, retrospectively evaluated efficacy and tolerability of adjuvant eribulin in patients with LPS not suitable for intensive chemotherapy in the routine clinical setting. PATIENTS AND METHODS: In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in five high risk LPS patients. RESULTS: Eribulin as treatment was administered to five patients with LPS following surgical resection. Median progression-free survival and overall survival were 12.3 months and 44.3 months, respectively. Toxicity was generally manageable, and grade 3+4 events were rare. CONCLUSION: Postoperative eribulin may be feasible in selected high risk LPS patients, who are not candidates for intensive chemotherapy regimens. Further prospective trials, however, are needed.

Doublet and Triplet Combinations of Eribulin, Fulvestrant, and Palbociclib in Preclinical Breast Cancer Models.

BACKGROUND/AIM: This study investigated in vivo synergism between eribulin and palbociclib in a breast cancer patient-derived xenograft (PDX) model, with expanded scope to include fulvestrant as a third drug. MATERIALS AND METHODS: Eribulin plus palbociclib combinations were tested in vitro in six cell lines each of estrogen receptor positive and triple-negative breast cancer, and in vivo in the OD-BRE-0192 PDX model using weekly eribulin plus 5×/week or 7×/week palbociclib (holiday or no-holiday schedules, respectively). When included as a third drug, fulvestrant was dosed weekly. RESULTS: In vitro, combining palbociclib with eribulin led to increased eribulin IC50s in 11 of 12 cell lines, suggesting that the drugs antagonized each other due to mutual exclusion of the mitotic and G1/S cell cycle block points for eribulin and palbociclib. An in vivo study in the OD-BRE-0192 PDX model compared weekly eribulin plus either palbociclib holiday or no-holiday schedules to gauge the importance of post-palbociclib cell cycle synchronization. Results showed no advantage of holiday over no-holiday schedules, arguing that differing pharmacokinetics of the drugs were sufficient to overcome cell cycle-based mechanistic antagonism. In vivo comparisons of doublet and triplet combinations of eribulin, palbociclib, and fulvestrant showed that all three doublets were superior to individual monotherapies, and that the triplet combination was markedly superior to all three doublets, being the only group to show tumor regression in 100% of the mice. CONCLUSION: Results show complex synergistic interactions between eribulin, fulvestrant, and palbociclib, and point to a particularly robust synergy when combining all three drugs.

Effects of Eribulin on the RNA Content of Extracellular Vesicles Released by Metastatic Breast Cancer Cells.

Extracellular vesicles (EVs) are small lipid particles secreted by almost all human cells into the extracellular space. They perform the essential function of cell-to-cell communication, and their role in promoting breast cancer progression has been well demonstrated. It is known that EVs released by triple-negative and highly aggressive MDA-MB-231 breast cancer cells treated with paclitaxel, a microtubule-targeting agent (MTA), promoted chemoresistance in EV-recipient cells. Here, we studied the RNA content of EVs produced by the same MDA-MB-231 breast cancer cells treated with another MTA, eribulin mesylate. In particular, we analyzed the expression of different RNA species, including mRNAs, lncRNAs, miRNAs, snoRNAs, piRNAs and tRNA fragments by RNA-seq. Then, we performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and miRNA-target identification. Our findings demonstrate the possible involvement of EVs from eribulin-treated cells in the spread of chemoresistance, prompting the design of strategies that selectively target tumor EVs.

Involvement of ferroptosis in eribulin-induced cytotoxicity in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a unique clinicopathological subtype of epithelial ovarian cancer that is resistant to standard chemotherapy. Eribulin, a microtubule dynamics inhibitor of halichondrin class, has unique effects in the cancer microenvironment such as induction of epithelization and reduction in metastatic potential in breast cancer cells; however, nothing is known about the effect of eribulin and the detailed mechanisms in OCCC. This study aimed to investigate the involvement of ferroptosis and its mechanism in the antitumor activity of eribulin in OCCC cells and a mouse xenograft model. We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor. Eribulin increased the levels of intracellular iron, reactive oxygen species (ROS), and lipid peroxides, and increased the mitochondrial membrane potential. Eribulin downregulated the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), and superoxide dismutase (SOD) activity. The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC.

Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer.

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. PATIENTS AND METHODS: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. RESULTS: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.

Clinicopathological and prognostic features of HER2-null and HER2-low advanced breast cancer treated with eribulin or capecitabine.

BACKGROUND: HER2-low populations constitute a heterogeneous group, and the cytotoxic anticancer agent efficacy based on HER2 status remains unclear. This study evaluated the clinicopathological features and outcomes of patients with advanced breast cancer showing HER2-low expression treated with eribulin or capecitabine, two treatment options after anthracycline and taxane treatment. METHODS: We retrospectively evaluated patients who were treated with eribulin or capecitabine between 2011 and 2015. HER2 status was evaluated according to the ASCO/CAP guidelines. RESULTS: No significant difference was observed in overall survival (OS; eribulin: hazard ratio [HR], 0.66; 95% CI 0.40-1.10; capecitabine: HR, 0.76; 95% CI 0.45-1.30) or progression-free survival (PFS; eribulin: HR, 1.13; 95% CI 0.72-1.78; capecitabine: HR, 0.90; 95% CI 0.56-1.44) between patients receiving eribulin (HER2-null: 35, HER2-low: 44) and those receiving capecitabine (HER2-null: 41, HER2-low: 33). Subgroup analysis revealed no significant differences in OS between the two groups in the hormone-positive and -negative populations for eribulin and capecitabine. HER2-null and HER2-low patients showed objective response rates (ORRs) of 22.5% and 9.1% (p = 0.09) overall, and 32.0% and 10.5% (p = 0.03), respectively, in hormone-positive cases among eribulin-treated patients. No response was observed in hormone-negative patients. Capecitabine treatment in HER2-null and HER2-low patients had overall ORRs of 26.8% and 15.2% (p = 0.23), respectively, with 27.3% and 16.1% (p = 0.28) for hormone-positive cases; and 25.0% and 0% (p = 1.0), respectively, for hormone-negative cases. CONCLUSIONS: Eribulin and capecitabine sensitivity may vary based on HER2 expression in patients with HER2-low and HER2-null breast cancer. Prognosis was similar between the HER2-low and the HER2-null groups.

Extensive Synergy Between Recombinant Methioninase and Eribulin Against Fibrosarcoma Cells But Not Normal Fibroblasts.

BACKGROUND/AIM: The aim of the present study was to determine the synergy of recombinant methioninase (rMETase) and the anti-tubulin agent eribulin on fibrosarcoma cells, in comparison to normal fibroblasts, in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells and HS27 human fibroblasts were used for in vitro experiments. Four groups were analyzed in vitro: No-treatment control; eribulin; rMETase; eribulin plus rMETase. Dual-color HT1080 cells which express red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize cytoplasmic and nuclear dynamics during treatment. RESULTS: Eribulin combined with rMETase greatly decreased the viability of HT 1080 cells. In contrast, eribulin combined with rMETase did not show synergy on Hs27 normal fibroblasts. Eribulin combined with rMETase also caused more fragmentation of the nucleus than all other treatments. CONCLUSION: The combination treatment of eribulin plus rMETase demonstrated efficacy on fibrosarcoma cells in vitro. In contrast, normal fibroblasts were resistant to this combination, indicating the potential clinical applicability of the treatment.

Optimal response to tislelizumab plus chemotherapy in metastatic triple-negative breast cancer: a case report and literature review.

Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.