A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer

Abstract

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m2 on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1–21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting

“…However, the results of the phase 2 clinical trial in Japan, which included patients with HER2-negative breast cancer who used eribulin as a first-line treatment, showed a more prolonged OS (35.9 months) than the result of this study [9]. This difference might be attributable to the relatively small number of patients (35 patients) included in the phase 2 study [9]. One phase 3 trial reported similar OS as in this study which was more prolonged in patients using eribulin (16.1 months) than in patients using capecitabine (13.5 months) when these were used as second-line treatment with a manageable safety profile [13].…”

“…Previously reported OS results included 16.1 months [13] Common Terminology Criteria for Adverse Events (version 4.0) all grade adverse drug reactions (ADRs) occurring in ≥5% of the patients in all groups are summarized a) One patient whose number of previous chemotherapy regimens was unknown was included in the analysis third or later-lines. However, the results of the phase 2 clinical trial in Japan, which included patients with HER2-negative breast cancer who used eribulin as a first-line treatment, showed a more prolonged OS (35.9 months) than the result of this study [9]. This difference might be attributable to the relatively small number of patients (35 patients) included in the phase 2 study [9].…”

“…Furthermore, TTF was reported as 4.2 months in this study compared with 3.91 months [23] and approximately 4 months (127 days) [16] in previous studies on eribulin as a first-, second-, third or later-line treatments. In comparison, 5.2 and 5.3 months [9] were reported in this and a previous study for eribulin as first-line treatment, respectively.…”

“…The efficacy and safety of eribulin as the first-or secondline treatment was not explored in randomized controlled trials. However, some clinical trials (mainly phase 2) and a realworld study reported the efficacy and safety of eribulin as a first-or second-line treatment [6][7][8][9][10][11][12][13][14][15]. Jacot et al reported the activities of eribulin among metastatic breast cancer patients in a multicenter national observational Epidemiological Strategy and Medical Economic (ESME) program in a realworld setting [14].…”

Neutropenia Associada ao Tratamento do Câncer de Mama: Revisão Integrativa da Literatura

“…Ou seja, os participantes que receberam as formulações genéricas tiveram os índices maiores de neutropenia 25 . Apenas um estudo avaliou o quimioterápico eribulina e apresentou mielotoxicidade com neutropenia grau 3 ou 4 superior a 50% 26 . Alguns estudos avaliaram outras diferentes combinações de medicamentos quimioterápicos, mas a neutropenia não foi avaliada como um fator isolado para cada medicamento.…”