title: Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients.
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.
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P. R. China. bhxu@hotmail.com
authors.forename: Bing-He
authors.initials: BH
authors.lastname: Xu
authors.forename: Ze-Fei
authors.initials: ZF
authors.lastname: Jiang
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Shao
authors.forename: Rong-Cheng
authors.initials: RC
authors.lastname: Luo
authors.forename: Xiao-Jia
authors.initials: XJ
authors.lastname: Wang
authors.forename: Dong-Geng
authors.initials: DG
authors.lastname: Liu
authors.forename: Winnie
authors.initials: W
authors.lastname: Yeo
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yu
authors.forename: Beth
authors.initials: B
authors.lastname: Newstat
authors.forename: Alka
authors.initials: A
authors.lastname: Preston
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Martin
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Chi
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D058534:Class I Phosphatidylinositol 3-Kinases; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012074:Remission Induction
chemical_list: D000069287:Capecitabine; D058534:Class I Phosphatidylinositol 3-Kinases; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D019869:Phosphatidylinositol 3-Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human