for Stage IVs-- proof herceptin still beneficial even after resistance 2 lapatinib

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Ann Oncol. 2011 Oct 29. [Epub ahead of print]
Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer.
Gori S, Montemurro F, Spazzapan S, Metro G, Foglietta J, Bisagni G, Ferzi A, Silva RR, Gamucci T, Clavarezza M, Stocchi L, Fabi A, Cognetti F, Torrisi E, Crivellari D.
Source
Department of Medical Oncology, S. Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia.
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