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 Ro, Sohee Park, Sung- Bae Kim, Tae You Kim, Young Hyuk Im, Sun Young Rha, Joo Seop Chung, Hanlim Moon, Sergio Santillana, Jungsil Ro, Sohee Park, Sung- Bae Kim, Tae You Kim, Young Hyuk Im, Sun Young Rha, Joo Seop Chung, Hanlim Moon, Sergio Santillana

Abstract

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

Methods: 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/m(2) daily in two divided doses, days 1-14, every 21 days and lapatinib 1250 mg once daily.

Results: 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.

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

Trial registration: ClinicalTrials.gov (NCT00338247).

Figures

Figure 1
Figure 1
Kaplan-Meier estimates for (A) brain PFS by hormone receptor (HR) status; (B) PFS by hormone receptor (HR) status; (C) OS by hormone receptor (HR) status; (D) brain PFS by prior capecitabine; (E) PFS by prior capecitabine; and (F) OS by prior capecitabine in patients with brain metastasis on entry.
Figure 2
Figure 2
In the overall population regardless of brain metastasis status, Kaplan-Meier estimates for (A) PFS by prior capecitabine; (B) OS by prior capecitabine; (C) PFS by hormone receptor (HR) status; (D) OS by HR status; (E) PFS by brain metastasis status in; (F) OS by brain metastasis status

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