Literature DB >> 22689807

Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study.

Kimberly L Blackwell1, Harold J Burstein, Anna Maria Storniolo, Hope S Rugo, George Sledge, Gursel Aktan, Catherine Ellis, Allison Florance, Svetislava Vukelja, Joachim Bischoff, José Baselga, Joyce O'Shaughnessy.   

Abstract

PURPOSE: Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. PATIENTS AND METHODS: Patients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit.
RESULTS: In this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metastatic sites, and less time from initial diagnosis until random assignment, were associated with improved OS. Incidence of adverse events was consistent with previously reported rates.
CONCLUSION: These data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.

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Year:  2012        PMID: 22689807     DOI: 10.1200/JCO.2011.35.6725

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


  188 in total

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