Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer
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Published:2008-12-01
Issue:34
Volume:26
Page:5544-5552
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Di Leo Angelo1, Gomez Henry L.1, Aziz Zeba1, Zvirbule Zanete1, Bines Jose1, Arbushites Michael C.1, Guerrera Stephanie F.1, Koehler Maria1, Oliva Cristina1, Stein Steven H.1, Williams Lisa S.1, Dering Judy1, Finn Richard S.1, Press Michael F.1
Affiliation:
1. From the “Sandro Pitigliani” Medical Oncology Unit, Prato, Italy; Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru; Allama Iqbal Medical College, Lahore, Pakistan; Riga Eastern University Hospital Latvian Oncology Centre, Rīga, Latvia; National Cancer Institute, Rio De Janeiro, Brazil; Medicine Development Center Oncology, GlaxoSmithKline, Collegeville, PA; Geffen School of Medicine at University of California, Los Angeles; and Norris Comprehensive Cancer Center, University of Southern...
Abstract
PurposeLapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2–positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2–negative and HER-2–uncharacterized MBC.Patients and MethodsWomen with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m2every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS).ResultsIn the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2–negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms.ConclusionPatients with HER-2–negative or HER-2–untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2–positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2–positive breast cancer patients.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Reference26 articles.
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