Open Access Highly Accessed Research article

Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

Jungsil Ro1*, Sohee Park1, Sung- Bae Kim2, Tae You Kim3, Young Hyuk Im4, Sun Young Rha5, Joo Seop Chung6, Hanlim Moon7 and Sergio Santillana7

Author Affiliations

1 National Cancer Center Hospital and Research Institute, Goyang, Gyeonggi-do, 410-769, Republic of Korea

2 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

3 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

4 Department of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea

5 Department of Internal Medicine, Severance Hospital, Seodaemun-gu, South Korea

6 Deparment of Medical Oncology, Pusan National University Hospital, Busan, Republic of Korea

7 Department of Medical (AP Oncology). GlaxoSmithKline Oncology, Seoul, Republic of Korea

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BMC Cancer 2012, 12:322  doi:10.1186/1471-2407-12-322

Published: 28 July 2012



To evaluate efficacy in patients with brain metastasis (BM) on entry into the lapatinib expanded access program (LEAP).


LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily.


Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS) was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88). In patients with BM, brain response was synchronized with systemic responses (P = 0.0001). Overall survival (OS) was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23). Multivariable analysis found hormone receptor positivity (P = 0.003) and clinical benefit rate (CBR) of combined systemic and brain disease (P < 0.0001) significantly associated with prolonged brain PFS, and CBR of combined systemic and brain disease (P = 0.03) and longer trastuzumab use (P = 0.047) associated with prolonged OS in patients with BM; prior capecitabine did not affect PFS or OS in patients with BM.


Lapatinib plus capecitabine is equally effective in patients with or without BM.

Trial registration (NCT00338247)

Brain Metastasis; HER2-positive Metastatic Breast Cancer; Lapatinib and Capecitabine Therapy; LEAP