Vinorelbine After Prior Treatment With Eribulin for Advanced Breast Cancer: A Single-Centre Experience Suggesting Cross-Resistance


      • Vinorelbine has very limited efficacy for patients with advanced breast cancer who have previously received an anthracycline, taxane and eribulin.
      • Vinorelbine is a modestly effective palliative chemotherapy for patients who have received prior anthracycline and taxane but not eribulin.



      The tubulin inhibitor, eribulin, improves survival for previously treated advanced breast cancer (ABC) compared to chemotherapy of physician's choice, including vinorelbine, an older anti-tubulin. Vinorelbine is commonly still used after eribulin, but potentially risks cross-resistance and its efficacy in this setting is unproven.

      Materials and Methods

      A retrospective analysis of all patients who received vinorelbine after prior eribulin (VAE) 2011-2015 and a parallel cohort of consecutive patients who received vinorelbine without prior eribulin (VWE) for previously treated ABC between 2005 and 2011. Patient demographics, histopathological features, treatment duration and responses were recorded. The primary endpoint was progression-free survival from date of first vinorelbine for each cohort. Secondary endpoints included radiological response rate, and overall survival (OS).


      Thirty-five VAE and 103 VWE patients were identified, all female, 71.4% and 78.6% were ER positive/HER2 negative, 8.6% and 6.8% HER2 positive, and 20.0% and 14.6% triple negative for VAE and VWE cohorts, respectively. The median number of lines of chemotherapy lines prior to vinorelbine was 4 (range 2-6) and 2 (range 0-4), respectively. Fifteen VAE patients (42.9%) received ≥1 line of chemotherapy between eribulin and vinorelbine. VAE and WWE Patients received a median of 3 cycles of vinorelbine (range 1-9 and 1-12, respectively). The median progression-free survival for VAE patients was 2.1 months and 2.0 months for VWE patients. No VAE patients were progression-free at 24 weeks, compared to 15.5% of VWE patients. Median OS from commencing vinorelbine was 4.3 months for VAE and 6.4 months for VWE patients.


      Vinorelbine was of limited benefit after prior eribulin in our study, suggesting cross-resistance. Even without prior eribulin, only 15% of patients experienced clinical benefit from vinorelbine monotherapy.



      ABC (Advanced breast cancer), TNBC (Triple negative breast cancer), IDC (Invasive ductal carcinoma), ILC (Invasive lobular carcinoma), PFS (progression-free survival), HR (Hazard ratio), CI (Confidence interval), TPC (Therapy of physician's choice), RMH (Royal Marsden Hospital), ER (Oestrogen receptor), VAE (Vinorelbine after eribulin), VWE (Vinorelbine without prior eribulin), PR (partial response), CR (complete response), SD (stable disease), OS (overall survival), CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography)
      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 to Clinical Breast Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Yuan P.
        • Hu X.
        • Sun T.
        • et al.
        Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: a randomised clinical trial.
        Eur J Cancer. 2019; 112: 57-65
        • Decker T.
        • Marschner N.
        • Muendlein A.
        • et al.
        VicTORia: a randomised phase II study to compare vinorelbine in combination with the mTOR inhibitor everolimus versus vinorelbine monotherapy for second-line chemotherapy in advanced HER2-negative breast cancer.
        Breast Cancer Res Treat. 2019; 176: 637-647
        • André F.
        • O’Regan R.
        • Ozguroglu M.
        • et al.
        Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
        Lancet Oncol. 2014; 15: 580-591
        • Harbeck N.
        • Huang C-S.
        • Hurvitz S.
        • et al.
        Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial.
        Lancet Oncol. 2016; 17: 357-366
        • Farhat F.
        • Kattan J.G.
        • Ghosn M.
        Oral vinorelbine in combination with trastuzumab as a first-line therapy of metastatic or locally advanced HER2-positive breast cancer.
        Cancer Chemother Pharmacol. 2016; 77: 1069-1077
        • Andersson M.
        • Lidbrink E.
        • Bjerre K.
        • et al.
        Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study.
        J Clin Oncol. 2011; 29: 264-271
        • 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
        • Wu Y.
        • Wang Q.
        • Zhang J.
        • et al.
        Incidence of peripheral neuropathy associated with eribulin mesylate versus vinorelbine in patients with metastatic breast cancer: sub-group analysis of a randomized phase III study.
        Support Care Cancer. 2020; 28: 3819-3829
        • Keller A.M.
        • Mennel R.G.
        • Georgoulias V.A.
        • et al.
        Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.
        J Clin Oncol. 2004; 22: 3893-3901
        • Abeloff M.D.
        Vinorelbine (Navelbine) in the treatment of breast cancer: a summary.
        Semin Oncol. 1995; 22 (discussion 41-4): 1-4
        • Loibl S.
        • O’Shaughnessy J.
        • Untch M.
        • et al.
        Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial.
        Lancet Oncol. 2018; 19: 497-509
        • 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
        • Vici P.
        • Di Lauro L.
        • Sergi D.
        • et al.
        A phase II trial of docetaxel and vinorelbine in patients with advanced breast cancer previously treated with anthracyclines.
        Oncology. 2008; 75: 175-181
        • Spano J.P.
        • Bouillet T.
        • Boaziz C.
        • et al.
        Phase II study of paclitaxel combined with vinorelbine in patients with advanced breast cancer.
        Am J Clin Oncol. 2004; 27: 317-321
        • Pallis A.G.
        • Boukovinas I.
        • Ardavanis A.
        • et al.
        A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer.
        Ann Oncol. 2012; 23: 1164-1169
        • Iaffaioli R.V.
        • Tortoriello A.
        • Facchini G.
        • et al.
        A phase II study of carboplatin and vinorelbine as second-line treatment for advanced breast cancer.
        Br J Cancer. 1995; 72: 1256-1258
        • Nolè F.
        • Catania C.
        • Sanna G.
        • et al.
        Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine for patients with metastatic breast cancer.
        Ann Oncol. 2006; 17: 322-329
        • Lorusso V.
        • Spada M.
        • Giampaglia M.
        • et al.
        Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC). A phase II study of the GOIM (Gruppo Oncologico dell’Italia Meridionale).
        Ann Oncol. 2006; 17: vii15-vii17
        • Finek J.
        • Holubec Jr., L.
        • Svoboda T.
        • et al.
        A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer.
        Anticancer Res. 2009; 29: 667-670
        • Jones A.
        • O’Brien M.
        • Sommer H.
        • et al.
        Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes.
        Cancer Chemother Pharmacol. 2010; 65: 755-763
        • Mao W.
        • Guan X.
        • Tucker S.
        • et al.
        Second-line combination chemotherapy with vinorelbine and capecitabine in patients with advanced breast cancer previously treated with anthracyclines and/or taxanes.
        Chemotherapy. 2011; 57: 71-76
        • Li S.
        • Meng W.
        • Zhang J.
        • et al.
        A randomized controlled Phase II trial of vinorelbine plus capecitabine versus docetaxel plus capecitabine in anthracycline-pretreated women with metastatic breast cancer.
        J Cancer Res Ther. 2020; 16: 1069-1076
        • Hess D.
        • Koberle D.
        • Thurlimann B.
        • et al.
        Capecitabine and vinorelbine as first-line treatment in elderly patients (>or =65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99).
        Oncology. 2007; 73: 228-237
        • Campone M.
        • Dobrovolskaya N.
        • Tjulandin S.
        • et al.
        A three-arm randomized phase II study of oral vinorelbine plus capecitabine versus oral vinorelbine and capecitabine in sequence versus docetaxel plus capecitabine in patients with metastatic breast cancer previously treated with anthracyclines.
        Breast J. 2013; 19: 240-249
        • Welt A.
        • Marschner N.
        • Lerchenmueller C.
        • et al.
        Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial.
        Breast Cancer Res Treat. 2016; 156: 97-107
        • Martin M.
        • Ramos-Medina R.
        • Bernat R.
        • et al.
        Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts.
        Sci Rep. 2021; 11: 7064-7076
        • Gorski J.W.
        • Zhang Z.
        • McCorckle J.R.
        • et al.
        Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance.
        Biomedicines. 2021; 9: 1021-1037
        • Kim Y.
        • Kim D.
        • Cao B.
        • et al.
        PDXGEM: patient-derived tumor xenograft-based gene expression model for predicting clinical response to anticancer therapy in cancer patients.
        BMC Bioinformatics. 2020; 21: 288-308