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.
Author(s): Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C,
Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J.
Affiliation(s): Department of Medicine/Medical Oncology, Duke University Medical Center, Durham,
NC 27710, USA. black034@mc.duke.edu
Publication date & source: 2012, J Clin Oncol. , 30(21):2585-92
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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