Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer

Nancy U. Lin, Lisa A. Carey, Minetta C Liu, Jerry Younger, Steven E. Come, Matthew Ewend, Gordon J. Harris, Elizabeth Bullitt, Annick D. Van Den Abbeele, John W. Henson, Xiaochun Li, Rebecca Gelman, Harold J. Burstein, Elizabeth Kasparian, David G. Kirsch, Ann Crawford, Fred Hochberg, Eric P. Winer

Research output: Contribution to journalArticle

330 Citations (Scopus)

Abstract

Purpose: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Patients and Methods: Patients had HER-2-positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. Results: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Conclusion: The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

Original languageEnglish (US)
Pages (from-to)1993-1999
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

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Breast Neoplasms
Neoplasm Metastasis
Brain
Brain Neoplasms
lapatinib
human ERBB2 protein
Tumor Burden
Epidermal Growth Factor Receptor
Fatigue
Diarrhea
Magnetic Resonance Imaging
Radiation
Safety
Survival
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. / Lin, Nancy U.; Carey, Lisa A.; Liu, Minetta C; Younger, Jerry; Come, Steven E.; Ewend, Matthew; Harris, Gordon J.; Bullitt, Elizabeth; Van Den Abbeele, Annick D.; Henson, John W.; Li, Xiaochun; Gelman, Rebecca; Burstein, Harold J.; Kasparian, Elizabeth; Kirsch, David G.; Crawford, Ann; Hochberg, Fred; Winer, Eric P.

In: Journal of Clinical Oncology, Vol. 26, No. 12, 2008, p. 1993-1999.

Research output: Contribution to journalArticle

Lin, NU, Carey, LA, Liu, MC, Younger, J, Come, SE, Ewend, M, Harris, GJ, Bullitt, E, Van Den Abbeele, AD, Henson, JW, Li, X, Gelman, R, Burstein, HJ, Kasparian, E, Kirsch, DG, Crawford, A, Hochberg, F & Winer, EP 2008, 'Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer', Journal of Clinical Oncology, vol. 26, no. 12, pp. 1993-1999. https://doi.org/10.1200/JCO.2007.12.3588
Lin, Nancy U. ; Carey, Lisa A. ; Liu, Minetta C ; Younger, Jerry ; Come, Steven E. ; Ewend, Matthew ; Harris, Gordon J. ; Bullitt, Elizabeth ; Van Den Abbeele, Annick D. ; Henson, John W. ; Li, Xiaochun ; Gelman, Rebecca ; Burstein, Harold J. ; Kasparian, Elizabeth ; Kirsch, David G. ; Crawford, Ann ; Hochberg, Fred ; Winer, Eric P. / Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 12. pp. 1993-1999.
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title = "Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer",
abstract = "Purpose: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Patients and Methods: Patients had HER-2-positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. Results: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6{\%}, 95{\%} conditional CI, 0.21{\%} to 26{\%}). Seven patients (18{\%}) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21{\%}) and fatigue (grade 3, 15{\%}). Conclusion: The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.",
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T1 - Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer

AU - Lin, Nancy U.

AU - Carey, Lisa A.

AU - Liu, Minetta C

AU - Younger, Jerry

AU - Come, Steven E.

AU - Ewend, Matthew

AU - Harris, Gordon J.

AU - Bullitt, Elizabeth

AU - Van Den Abbeele, Annick D.

AU - Henson, John W.

AU - Li, Xiaochun

AU - Gelman, Rebecca

AU - Burstein, Harold J.

AU - Kasparian, Elizabeth

AU - Kirsch, David G.

AU - Crawford, Ann

AU - Hochberg, Fred

AU - Winer, Eric P.

PY - 2008

Y1 - 2008

N2 - Purpose: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Patients and Methods: Patients had HER-2-positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. Results: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Conclusion: The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

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