Document Detail


A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer.
MedLine Citation:
PMID:  23283526     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This phase II study (VEG20007; NCT00347919) with randomized and open-label components evaluated first-line lapatinib plus pazopanib therapy and/or lapatinib monotherapy in patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced/metastatic breast cancer. Patients were enrolled sequentially into two cohorts: Cohort 1, patients were randomly assigned to lapatinib 1,000 mg plus pazopanib 400 mg or lapatinib 1,500 mg monotherapy; Cohort 2, patients received lapatinib 1,500 mg plus pazopanib 800 mg. The primary endpoint was week-12 progressive disease rate (PDR) for Cohort 1. The principal secondary endpoint was week-12 response rate (RR) for Cohort 2. Efficacy was assessed in patients with centrally confirmed HER2 positivity (modified intent-to-treat population [MITT]). The study enrolled 190 patients (Cohort 1, combination n = 77, lapatinib n = 73; Cohort 2, n = 40). The MITT population comprised n = 141 (Cohort 1) and n = 36 (Cohort 2). In Cohort 1, week-12 PDRs were 36.2 % (combination) versus 38.9 % (lapatinib; P = 0.37 for the difference). Week-12 RRs were 36.2 % (combination) versus 22.2 % (lapatinib). In Cohort 2, week-12 RR was 33.3 %. In Cohort 1, grade 3/4 adverse events (AEs) included diarrhea (combination, 9 %; lapatinib, 5 %) and hypertension (combination, 5 %; lapatinib, 0 %). Grades 3/4 AEs in Cohort 2 included diarrhea (40 %), hypertension (5 %), and fatigue (5 %). Alanine aminotransferase elevations >5 times the upper limit of normal occurred in Cohort 1 (combination, 18 %; lapatinib, 5 %) and Cohort 2 (20 %). Upon conclusion, the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy, although RR was increased. Toxicity was higher with the combination, including increased diarrhea and liver enzyme elevations.
Authors:
Stephen R D Johnston; Henry Gómez; Salomon M Stemmer; Maria Richie; Michael Durante; Lini Pandite; Vicki Goodman; Dennis Slamon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  -     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Fulham Road, Chelsea, London, SW3 6JJ, UK, stephen.johnston@rmh.nhs.uk.
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