Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

Abstract

BACKGROUND:

Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting.

METHODS:

Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data.

RESULTS:

Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia.

CONCLUSION:

EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.

• Authors: Mélodie Dell'Ova, Eléonora De Maio, Séverine Guiu, Lise Roca, Florence Dalenc, Anna Durigova, Frédéric Pinguet, Khedidja Bekhtari, William Jacot, Stéphane Pouderoux
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 659 (Oct 08 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 26449988 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Furans
• Ketones
• Taxoids
• eribulin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacology, therapeutic use)
• Biomarkers, Tumor
• Breast Neoplasms (diagnosis, drug therapy, etiology, mortality)
• Drug Resistance, Neoplasm
• Female
• Furans (pharmacology, therapeutic use)
• Humans
• Ketones (pharmacology, therapeutic use)
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Taxoids (pharmacology)
• Treatment Outcome
• Young Adult