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Ann Oncol. 2012 Jun;23(6):1436-41. doi: 10.1093/annonc/mdr474. Epub 2011 Oct 29.

Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer.

Author information

1
Department of Medical Oncology, S. Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia. stefania.gori@tin.it

Abstract

BACKGROUND:

Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells.

PATIENTS AND METHODS:

Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression.

RESULTS:

Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5-10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2-5.6) and overall survival (OS) 19.4 months (95% CI 14.0-25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021).

CONCLUSION:

Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.

PMID:
22039084
DOI:
10.1093/annonc/mdr474
[Indexed for MEDLINE]
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