Eribulin in advanced breast cancer: safety, efficacy and new perspectives.

Eribulin is a synthetic analog of halichondrin B belonging to microtubule-targeted agents with a distinct mechanism of inhibition of microtubule dynamics. This molecule has multiple nonmitotic effects on tumor biology, exhibiting effects on epithelial-mesenchimal transition and tumor vasculature. We review here preclinical and clinical studies on eribulin. The mitotic and nonmitotic effects together with its favorable safety profile make eribulin a unique drug with high potential in the treatment of metastatic breast cancer. The new emphasis of eribulin mechanism of action on vascular remodeling, microenvironment modifications and reversal of epithelial-mesenchimal transition paves the way to rethinking the use of the drug in an immunological perspective.

Patients with cancer and hospital admissions: disease trajectory and strategic choices.

OBJECTIVES: Hospital admission (HA) in cancer history is a common, repeated and frequently unplanned event. The emergency departments (EDs) and the oncological outpatient service (OOS) are the ordinary way of entry. We studied the reasons of admission, pathways of access and discharge and prognostic factors in a population of admitted patients with cancer. METHODS: The health records of the admitted patients in the oncological ward of a referral hospital in a 6-month period were retrieved and analysed. The characteristics of those admitted in the last 3 months of life were compared with the other group. RESULTS: Among the 147 HA, 79.5% were unplanned, 48.9% passing through the ED and 30.6% through the OOS; 56.5% were due to cancer-related symptoms; 50.3% occurred in the last 3 months of life. Median overall survival was 90 days (95% IC 53.1-126.9). Independent prognostic factors for survival were: being admitted for symptoms, referral through the ED and not being discharged at home. CONCLUSIONS: Hospital is a turning point in the cancer care pathway. Patients needing HA have a dismal prognosis, half of them being in the last 3 months of life. This group can be identified using universally available variables.

Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers.

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan-Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258-0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054-0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306-0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130-0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers.

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

BACKGROUND: Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor ß (TGF-ß) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin. METHODS: TGF-ß, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome. RESULTS: In the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD within the fourth course of treatment, compared with patients without progression. TGF-ß and IL-8 above the median and IL-21 below the median at T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-ß or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-ß changes at T1 correlated with survival. At TPD, TGF-ß significantly increased in all patients. CONCLUSIONS: We observed a significant correlation between TGF-ß decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.

Treating patients with cancer amidst the COVID-19 pandemic: experience of a regional hospital in the Piedmont region in northern Italy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is posing an unprecedented dilemma to oncologists worldwide, forcing them to decide whether to continue or suspend treatments in order to protect their most vulnerable patients from infection. After the first report from China, the outbreak spread rapidly worldwide. To, date no clear indications on how to treat patients with cancer with COVID-19 infection are available. METHODS: We report data on 21 patients with cancer referred to a single medical oncology unit of a general hospital from mid-March to April 23, 2020. RESULTS: Nine patients were on active cancer therapy during the infection and all stopped medical treatments. Overall 8 patients developed pneumonia and 6 patients died of COVID-19. CONCLUSION: The management of patients with cancer during the pandemic should be carefully balanced and discussed among oncologists and other key professionals involved in the treatment of this vulnerable group of patients, in order to balance the risk of treatment and the risk of infection.

Eribulin in pretreated metastatic breast cancer patients: results of the TROTTER trial-a multicenter retrospective study of eribulin in real life.

This retrospective multicenter analysis was aimed to evaluate clinical activity and tolerability of eribulin in pretreated metastatic breast cancer patients in clinical practice. Patients treated with eribulin from January 2012 to July 2013 were enrolled in the observational study from 10 italian hospitals. Tumor and toxicity evaluation were performed according to Agenzia Italiana Farmaco. One-hundred and thirteen patients were included in the study. Median age 62 years old. 71.7 % of the patients had visceral involvement and the majority had a burden of disease involving two or more organs with a median number of 2 (1-6). The median number of previous chemotherapy regimens for advanced disease was 3 (1-10). Median number of eribulin cycles was 4 (1-27). Overall response rate was 24 % (95 % CI 16.0-31.8). Clinical benefit rate, was 35.4 % (95 % CI 26.6-44.2). At a median follow-up of 29.6 months (8.3-41.9) the median progression free survival was 3.3 months (0.6-26.7; 95 % CI 2.4-4.2), and the median overall survival 11.6 months (0.6-33.3; 95 % CI 8.7-14.5). No correlation was recorded between subtypes in terms of ORR and CBR. Toxicity was manageable. Main common grade 3-4 toxicities were neutropenia (19.4 %), febrile neutropenia (0.9 %), asthenia (3.5 %), abnormal liver function test (1.8 %), stomatitis (0.9 %). Our results confirm that treatment with eribulin is feasible and safe in real-world patients.