Advertisement

Phase II, Multicenter, Single-arm Trial of Eribulin as First-line Therapy for Patients With Aggressive Taxane-pretreated HER2-Negative Metastatic Breast Cancer: The MERIBEL Study

Published:December 19, 2018DOI:https://doi.org/10.1016/j.clbc.2018.12.012

      Abstract

      Background

      Eribulin has efficacy in patients with progression after ≥ 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors.

      Patients and Methods

      Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received ≥ 1 dose of eribulin.

      Results

      The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia.

      Conclusion

      Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Breast Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cancer Genome Atlas Network
        Comprehensive molecular portraits of human breast tumours.
        Nature. 2012; 490: 61-70
        • Perou C.M.
        • Sørlie T.
        • Eisen M.B.
        • et al.
        Molecular portraits of human breast tumours.
        Nature. 2000; 406: 747-752
        • Cardoso F.
        • Costa A.
        • Norton L.
        • et al.
        1st International consensus guidelines for advanced breast cancer (ABC 1).
        Breast. 2012; 21: 242-252
        • Hortobagyi G.N.
        • Stemmer S.M.
        • Burris H.A.
        • et al.
        Ribociclib as first-line therapy for HR-positive, advanced breast cancer.
        N Engl J Med. 2016; 375: 1738-1748
        • Finn R.S.
        • Martin M.
        • Rugo H.S.
        • et al.
        Palbociclib and letrozole in advanced breast cancer.
        N Engl J Med. 2016; 375: 1925-1936
        • Cardoso F.
        • Costa A.
        • Norton L.
        • et al.
        ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2).
        Breast. 2014; 23: 489-502
        • Cardoso F.
        • Costa A.
        • Senkus E.
        • et al.
        3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3).
        Ann Oncol. 2017; 28: 16-33
        • Baselga J.
        • Cortés J.
        • Kim S.-B.
        • et al.
        Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.
        N Engl J Med. 2012; 366: 109-119
        • Gelmon K.
        • Dent R.
        • Mackey J.R.
        • Laing K.
        • McLeod D.
        • Verma S.
        Targeting triple-negative breast cancer: optimising therapeutic outcomes.
        Ann Oncol. 2012; 23: 2223-2234
        • Piccart-Gebhart M.J.
        • Burzykowski T.
        • Buyse M.
        • et al.
        Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.
        J Clin Oncol. 2008; 26: 1980-1986
        • Sledge G.W.
        • Neuberg D.
        • Bernardo P.
        • et al.
        Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193).
        J Clin Oncol. 2003; 21: 588-592
        • Palmieri C.
        • Krell J.
        • James C.R.
        • et al.
        Rechallenging with anthracyclines and taxanes in metastatic breast cancer.
        Nat Rev Clin Oncol. 2010; 7: 561-574
        • Cortes J.
        • O’Shaughnessy J.
        • Loesch D.
        • et al.
        Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study.
        Lancet. 2011; 377: 914-923
        • Kaufman P.A.
        • Awada A.
        • Twelves C.
        • et al.
        Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane.
        J Clin Oncol. 2015; 33: 594-601
        • Kuznetsov G.
        • TenDyke K.
        • Yu M.
        • Littlefield B.
        Antiproliferative effects of halichondrin B analog eribulin mesylate (E7389) against paclitaxel-resistant human cancer cells in vitro.
        Mol Cancer Ther. 2007; 6: C58
        • Inoue K.
        • Saito T.
        • Okubo K.
        • et al.
        Phase II clinical study of eribulin monotherapy in Japanese patients with metastatic breast cancer who had well-defined taxane resistance.
        Breast Cancer Res Treat. 2016; 157: 295-305
        • Cortes J.
        • Vahdat L.
        • Blum J.L.
        • et al.
        Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine.
        J Clin Oncol. 2010; 28: 3922-3928
        • Vahdat L.T.
        • Pruitt B.
        • Fabian C.J.
        • et al.
        Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
        J Clin Oncol. 2009; 27: 2954-2961
        • Ershler W.B.
        Capecitabine monotherapy: safe and effective treatment for metastatic breast cancer.
        Oncologist. 2006; 11: 325-335
        • Sparano J.A.
        • Vrdoljak E.
        • Rixe O.
        • et al.
        Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
        J Clin Oncol. 2010; 28: 3256-3263
        • Llombart-Cussac A.
        • Pivot X.
        • Biganzoli L.
        • et al.
        A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA trial.
        Breast. 2014; 23: 656-662
        • Goldhirsch A.
        • Gelber R.D.
        • Castiglione M.
        Relapse of breast cancer after adjuvant treatment in premenopausal and perimenopausal women: patterns and prognoses.
        J Clin Oncol. 1988; 6: 89-97
        • Yoshida T.
        • Ozawa Y.
        • Kimura T.
        • et al.
        Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states.
        Br J Cancer. 2014; 110: 1497-1505
        • Funahashi Y.
        • Okamoto K.
        • Adachi Y.
        • et al.
        Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models.
        Cancer Sci. 2014; 105: 1334-1342
        • Dienstmann R.
        • Braña I.
        • Rodon J.
        • Tabernero J.
        Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on EGFR and VEGF inhibiting anticancer drugs.
        Oncologist. 2011; 16: 1729-1740
        • Yamanaka T.
        • Matsumoto S.
        • Teramukai S.
        • Ishiwata R.
        • Nagai Y.
        • Fukushima M.
        Predictive value of chemotherapy-induced neutropenia for the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma.
        Br J Cancer. 2007; 97: 37-42
        • Kishida Y.
        • Kawahara M.
        • Teramukai S.
        • et al.
        Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer: results from Japan Multinational Trial Organization LC00-03.
        Br J Cancer. 2009; 101: 1537-1542
        • Cortes J.
        • Hudgens S.
        • Twelves C.
        • et al.
        Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-label randomized phase 3 trial.
        Breast Cancer Res Treat. 2015; 154: 509-520