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 Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript 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. 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%). Patients and Methods-Patients 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.

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies

“…In this study, 10 patients had brain metastases at baseline and of these 8 experienced either systemic PR or SD, indicating that lapatinib monotherapy is efficacious in HER2-positive BC patients with brain metastases, thus supporting previous reports (Lin et al, 2008).…”

Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases – the UK experience

“…More recently, there have been further reports of responses to lapatinib-based therapy. After an initial singlecentre phase II study of lapatinib monotherapy in patients with HER2-positive breast cancer who developed progressive CNS metastases after prior loco-regional therapy (Lin et al, 2008), a larger multicentre phase II study involving 242 patients reported a 6% CNS ORR to lapatinib alone (Lin et al, 2009). In an exploratory analysis, a further 21% patients experienced a X20% volumetric reduction in CNS lesions, with many having significant improvement in neurological symptoms.…”

“…A phase II study with single agent lapatinib 750 mg bid was undertaken in patients with HER2-positive CNS metastases who had shown progression in their brain after earlier whole-brain radiotherapy (WBRT), and clinical and radiological responses were observed (Lin et al, 2008). Subsequently, a larger multicentre phase 2 study involving 242 patients recently reported a 6% CNS objective response rate to lapatinib alone (defined as X50% volumetric reduction of CNS lesion(s) (Lin et al, 2009).…”

AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018

“…Therefore, clinically, BMs are a highly relevant problem. Despite this, only limited data are available for opti mal treatment strategies in breast cancer patients, since most studies on BMs involved other tumor entities [30][31][32][33][34][35][36]. It is therefore encouraged to register patients with central nervous system (CNS) metastases diagnosed in Germany retrospec tively and prospectively in a collaborative registry study.…”