Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients

Bing-He Xu, Ze-Fei Jiang, Daniel Chua, Zhi-Min Shao, Rong-Cheng Luo, Xiao-Jia Wang, Dong-Geng Liu, Winnie Yeo, Shi-Ying Yu, Beth Newstat, Alka Preston, Anne-Marie Martin, Hai-Dong Chi, Li Wang, Bing-He Xu, Ze-Fei Jiang, Daniel Chua, Zhi-Min Shao, Rong-Cheng Luo, Xiao-Jia Wang, Dong-Geng Liu, Winnie Yeo, Shi-Ying Yu, Beth Newstat, Alka Preston, Anne-Marie Martin, Hai-Dong Chi, Li Wang

Abstract

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

Conflict of interest statement

Conflicts of Interest: Winnie Yeo is an advisory board member and received honoraria from GlaxoSmithkline. Beth Newstat, Anne-Marie Martin, and Alka Preston are employees and shareholders of GlaxoSmithkline. Hai-Dong Chi and Li Wang are employees of GlaxoSmithkline China. Bing-He Xu, Ze-Fei Jiang, Daniel Chua, Zhi-Min Shao, Rong-Cheng Luo, Xiao-Jia Wang, Dong-Geng Liu, and Shi-Ying Yu have no conflicts of interest.

Unique Trial Number: NCT00508274

Trial Registration Date: July 26th, 2007

Figures

Figure 1.. Kaplan-Meier curve for progression-free survival…
Figure 1.. Kaplan-Meier curve for progression-free survival (PFS) of 52 patients with HER2-positive metastatic breast cancer treated with lapatinib plus capecitabine. Median PFS was 6.34 months (95% confidence interval, 4.93–9.82 months).
Figure 2.. Comparison of best response in…
Figure 2.. Comparison of best response in patients with wild-type PIK3CA versus mutant PIK3CA. The numbers above each bar indicate the percent of patients with each best response. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

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Source: PubMed

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