Abstract
Background
Eribulin plus gemcitabine improves progression-free survival in chemotherapy-naive metastatic breast cancer patients, but its efficacy in second-line or later treatment remains unclear.
Methods
This single-arm, phase II study was conducted at 13 Chinese medical centers. Eligible patients had histologically confirmed human epidermal growth factor receptor 2 negative metastatic breast cancer and had received at least one prior taxane-containing chemotherapy regimen and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Progression-free survival, objective response rate and disease control rate were assessed. Adverse events were also recorded.
Results
Here we show 70 patients took part in this study (71.4% hormone receptor positive/HER2 negative). Patients had received a median of three prior lines of systemic treatment. Overall, 48.6% have significant tumor shrinkage, 92.9% have tumor control, and median time without disease progression is 7.2 months (95% confidence interval, 5.5-10.9). Median time without disease progression is 8.4 months (hormone receptor positive) vs. 6.3 months (triple-negative, p = 0.1849). Grade 3–4 side effects mostly affect blood cells and are manageable.
Conclusions
Eribulin plus gemcitabine is effective and well-tolerated in patients with HER2-negative metastatic breast cancer needing second-line or later treatment, providing a valuable treatment option.
Plain language summary
People with advanced breast cancer that is HER2-negative often run out of treatment options after their first therapy. A drug combination called eribulin and gemcitabine works well as an initial treatment, but we didn’t know if it could help later on. To find out, we ran a study in 13 hospitals in China with 70 patients. They received both drugs every three weeks, and we tracked how their cancer responded and what side effects they had. Almost half of the patients saw their tumours shrink, and most had their cancer under control for an average of about seven months. Side effects, mainly related to blood counts, were manageable. These results suggest this drug combination could give people with advanced breast cancer another effective option.
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Data availability
Source data underlying Figs. 1–6 can be accessed from Supplementary Data 1.
References
Sung, H.A.-O. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, pp 1542–4863 (Electronic).
Xia et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants, pp 2542–5641 (Electronic).
Waks A. G. & Winer E. P. Breast Cancer Treatment: A Review. pp 1538–3598 (Electronic).
Itani, N., Grogan, N., Mott, S. & Phadke, S. Metastatic presentations of previously treated early-stage breast cancer patients and association with survival. Clin. Breast Cancer 20, 209–214 (2020).
Karihtala, P.A.-O., Jääskeläinen, A., Roininen, N. & Jukkola, A. Prognostic factors in metastatic breast cancer: a prospective single-centre cohort study in a Finnish University Hospital, pp 2044–6055 (Electronic).
Barni S. & Mandalà M. Chemotherapy for metastatic breast cancer, pp 1569–8041 (Electronic).
Lin, P. H. & Laliotis, G. The present and future of clinical management in metastatic breast cancer. J. Clin. Med. 11, 5891 (2022).
Jerusalem, G., Rorive, A. & Collignon, J. Chemotherapy options for patients suffering from heavily pretreated metastatic breast cancer, pp 1744–8301 (Electronic).
Pereira, R. B. et al. Marine-derived anticancer agents: clinical benefits, innovative mechanisms, and new targets. Mar. Drugs 17, 329–349 (2019).
Oya, K. et al. Eribulin mesylate exerts antitumor effects via CD103. Oncoimmunology 12, 2218782 (2023).
Wan, M. C. et al. Biomaterials from the sea: future building blocks for biomedical applications, pp 2452–199X (Electronic).
Perez-Garcia, J. M. & Cortes, J. The safety of eribulin for the treatment of metastatic breast cancer. Expert Opin. Drug Saf. 18, 347–355 (2019).
Funahashi, Y. et al. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models, pp 1349–7006 (Electronic).
Sachdev, P., Ronen, R., Dutkowski, J. & Littlefield, B. A. Systematic analysis of genetic and pathway determinants of eribulin sensitivity across 100 human cancer cell lines from the cancer cell line encyclopedia (CCLE). Cancers 14, 4532–4552 (2022).
McIntyre, K. et al. Phase 2 study of eribulin mesylate as first-line therapy for locally recurrent or metastatic human epidermal growth factor receptor 2-negative breast cancer. Breast Cancer Res. Treat. 146, 321–328 (2014).
De Luca, R., Alù, M., Genova, G., Grassadonia, A. & Cicero, G. Use of Eribulin mesylate as second-line therapy in elderly patients with HER/2 negative metastatic breast cancer (MBC): efficacy, tolerability and Quality of Life. Eur. Rev. Med Pharm. Sci. 24, 12727–12734 (2020).
Smith, J. et al. Phase II study of eribulin mesylate administered biweekly in patients with human epidermal growth factor receptor-2-negative metastatic breast cancer. Clin. Breast Cancer 20, 160–167 (2020).
Kaufman, P. A. 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. 33, 594–601 (2015).
Cortes, J. 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 377, 914–923 (2011).
Gesto, D. S., Cerqueira, N. M., Fernandes, P. A. & Ramos, M. J. Gemcitabine: a critical nucleoside for cancer therapy. Curr. Med Chem. 19, 1076–1087 (2012).
Jones, J. et al. Gemcitabine for the treatment of metastatic breast cancer. Health Technol. Assess. 13, 1–7 (2009).
Park, Y. H. et al. Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. Eur. J. Cancer 86, 385–393 (2017).
Kim, J. Y. et al. Quality of life outcomes including neuropathy-associated scale from a phase II, multicenter, randomized trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy for HER2-negative metastatic breast cancer: Korean Cancer Study Group Trial (KCSG BR13-11). Cancer Commun. (Lond.) 39, 29 (2019).
Yamamura, J. et al. Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015. Chemotherapy 62, 307–313 (2017).
Rugo, H. S. et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J. Clin. Oncol. 40, 3365–3376 (2022).
Miller, K. D. et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J. Clin. Oncol. 23, 792–799 (2005).
Zhu, A. et al. Phase II study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA. Cancer Biol. Med. 18, 875–887 (2021).
Lee, K. S., Park, I. H., Nam, B. H. & Ro, J. Phase II study of irinotecan plus capecitabine in anthracycline- and taxane-pretreated patients with metastatic breast cancer. Invest. N. Drugs 31, 152–159 (2013).
Herrscher, H. et al. Fulvestrant and palbociclib combination in heavily pretreated hormone receptor-positive, HER2-negative metastatic breast cancer patients. Breast Cancer Res. Treat. 179, 371–376 (2020).
Modi, S. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N. Engl. J. Med. 387, 9–20 (2022).
Twelves, C. et al. A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine. Br. J. Cancer 120, 579–586 (2019).
Zhang, P. et al. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol. 18, 371–383 (2017).
Garrone, O. et al. Eribulin in advanced breast cancer: safety, efficacy and new perspectives. Future Oncol. 13, 2759–2769 (2017).
Heinemann, V. Gemcitabine in metastatic breast cancer. Expert Rev. Anticancer Ther. 5, 429–443 (2005).
Ferrazzi, E. & Stievano, L. Gemcitabine: monochemotherapy of breast cancer. Ann. Oncol. 17, v169–v172 (2006).
Pellegrino, B. et al. Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). ESMO Open 6, 100019 (2021).
Finn, R. S. et al. Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18). Breast Cancer Res Treat. 183, 419–428 (2020).
Slamon, D. J. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann. Oncol. 32, 1015–1024 (2021).
Bardia, A. et al. Phase I/II trial of exemestane, ribociclib, and everolimus in women with HR(+)/HER2(-) advanced breast cancer after progression on CDK4/6 inhibitors (TRINITI-1). Clin. Cancer Res. 27, 4177–4185 (2021).
Kalinsky, K. et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial. J. Clin. Oncol. 41, 4004–4013 (2023).
Cortes, J. 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. 28, 3922–3928 (2010).
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Xiaolu Xu, Jincai Zhong, Hong Lin, Hong Wang, and Jinhui Ye contributed equally to this work. Xiaolu Xu: Conceptualization, Patient recruitment (leading enrollment at the affiliated institution), Clinical follow-up, Data collection and verification, Writing—Original Draft. Jincai Zhong: Patient recruitment (key enrollment at the affiliated institution), Clinical follow-up, Adverse event documentation, Data curation. Hong Lin: Patient recruitment (major enrollment at the affiliated institution), Clinical follow-up, Data collection, Adverse event monitoring. Hong Wang: Patient recruitment (core enrollment at the affiliated institution), Clinical follow-up, Sample management, Data collection. Jinhui Ye: Patient recruitment (primary enrollment at the affiliated institution), Clinical follow-up, Treatment implementation supervision, Data organization. Caiwen Du: Data collection, Data sorting, Statistical analysis support. Zhihui Wang: Resources (study site coordination), Patient screening, Clinical follow-up assistance, Data supplementary collection. Guorong Zou: Resources (institutional collaboration), Patient recruitment support, Sample storage management, Clinical follow-up. Jie Ouyang: Patient eligibility assessment, Clinical follow-up, Data collection and supplementary. Gengsheng Yu: Data curation, Data sorting, and Table construction support. Yongxia Wang: Patient recruitment assistance, Clinical follow-up, and Adverse event documentation. Luzhen Li: Patient screening, Clinical follow-up, Data collection. Fei Xu: Literature retrieval support, Patient recruitment assistance, Data verification. Shien Cui: Methodology support, Treatment protocol standardization, Clinical follow-up guidance. Mei Xiao*: Supervision, Project administration, Funding acquisition, Writing—Review & Editing, Final paper approval. Peijian Peng*: Supervision, Conceptualization, Study design, Data analysis oversight, Writing— Review & Editing, Final paper approval. *Corresponding authors.
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Communications Medicine thanks Toshinari Yamashita, Wei Jin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Xu, X., Zhong, J., Lin, H. et al. Efficacy and safety of eribulin plus gemcitabine as second-line treatment for recurrent HER2-negative breast cancer: a phase II, single-arm, open-label trial. Commun Med (2026). https://doi.org/10.1038/s43856-026-01483-z
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DOI: https://doi.org/10.1038/s43856-026-01483-z
