Benefit of eribulin in a patient with HER2.sup.+ breast cancer who progressed after trastuzumab and lapatinib: a case report

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From: Future Oncology(Vol. 11, Issue 15s)
Publisher: Future Medicine Ltd.
Document Type: Clinical report
Length: 2,705 words
Lexile Measure: 1490L

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Author(s): Claudia Casanova [*] aff1 , Alberto Verlicchi aff1 , Valentina Mazza aff1 , Claudio Dazzi aff1

KEYWORDS

eribulin mesylate; HER2+ breast cancer patient; trastuzumab

The HER2 was identified a quarter of century ago as a marker of poor prognosis in breast cancer, and it is overexpressed and/or amplified in about 15% of breast cancer patients [1 ]. Since 1998, antibody therapy targeting the HER2 pathway has been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic disease. Later on, in 2005, evidence of improvement in disease-free survival and OS from the first generation of trastuzumab adjuvant trials became available [2,3 ]. However, approximately 15% of patients develop metastatic disease despite trastuzumab-based adjuvant chemotherapy.

A randomized Phase III trial reported that patients receiving capecitabine plus lapatinib, an oral tyrosine kinase inhibitor of ERB-2 and ERB-1, had an advantage in terms of time to progression over patients receiving capecitabine monotherapy [4 ]. Based on these results, in March 2007, the combination of lapatinib and capecitabine was approved by the US FDA for the treatment of patients with HER2+ metastatic breast cancer who had received prior therapy including anthracyclines, taxanes and trastuzumab.

Eribulin mesylate is a synthetic analog of halichondrin B (a polyether macrolide isolated from a marine sponge). It is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. In 2011, Cortes et al . reported the results of a Phase III trial of patients affected from metastatic breast cancer that compared eribulin mesilate with treatment of physician's choice (TPC). Patients enrolled in this trial had received between two and five previous chemotherapy regimens, including an anthracycline and a taxane. Eribulin showed a significant and clinically meaningful improvement in OS compared with TPC in women with heavily pretreated metastatic breast cancer [5 ]. PFS was also increased in the eribulin arm compared with the TPC arm: 3.7 (95% CI: 3.3-3.9) versus 2.3 months (95% CI: 2.1-3.4).

To our knowledge, specific trials regarding treatment with monotherapy eribulin mesylate in HER2+ metastatic breast cancer have not been published to date. A recent multicenter Phase II study investigated the use of eribulin in combination with trastuzumab as first-line treatment for recurrent or metastatic HER2 + breast cancer patients. The results of the study suggest that the combination therapy is an acceptable therapeutic option in this group of patients. Median overall response rate was 71%, median time to relapse 1.3 months and PFS 11.6 months. The safety profile was also considered acceptable and the most common grade 3/4 adverse events were neutropenia, peripheral neuropathy, fatigue and febrile neutropenia [6 ].

A recent published analysis of pooled data from two Phase III trials reported that women with HER2-negative disease showed the most significant improvement in OS after eribulin treatment; however, the analysis also showed that all subgroups of patients assessed benefited from eribulin in terms of OS [ 7 ]. Few data regarding HER2-positive patients were obtained in the subgroup analysis of Phase II and III trials, with an advantage in OS and...

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Gale Document Number: GALE|A423986989