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09-19-2013, 10:36 AM
J Clin Oncol. (http://www.ncbi.nlm.nih.gov/pubmed/22689807#) 2012 Jul 20;30(21):2585-92. doi: 10.1200/JCO.2011.35.6725. Epub 2012 Jun 11.
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.
Blackwell KL (http://www.ncbi.nlm.nih.gov/pubmed?term=Blackwell%20KL%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Burstein HJ (http://www.ncbi.nlm.nih.gov/pubmed?term=Burstein%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Storniolo AM (http://www.ncbi.nlm.nih.gov/pubmed?term=Storniolo%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Rugo HS (http://www.ncbi.nlm.nih.gov/pubmed?term=Rugo%20HS%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Sledge G (http://www.ncbi.nlm.nih.gov/pubmed?term=Sledge%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Aktan G (http://www.ncbi.nlm.nih.gov/pubmed?term=Aktan%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Ellis C (http://www.ncbi.nlm.nih.gov/pubmed?term=Ellis%20C%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Florance A (http://www.ncbi.nlm.nih.gov/pubmed?term=Florance%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Vukelja S (http://www.ncbi.nlm.nih.gov/pubmed?term=Vukelja%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Bischoff J (http://www.ncbi.nlm.nih.gov/pubmed?term=Bischoff%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Baselga J (http://www.ncbi.nlm.nih.gov/pubmed?term=Baselga%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), O'Shaughnessy J (http://www.ncbi.nlm.nih.gov/pubmed?term=O%27Shaughnessy%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807).
Source
Department of Medicine/Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA. black034@mc.duke.edu
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.
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.
Blackwell KL (http://www.ncbi.nlm.nih.gov/pubmed?term=Blackwell%20KL%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Burstein HJ (http://www.ncbi.nlm.nih.gov/pubmed?term=Burstein%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Storniolo AM (http://www.ncbi.nlm.nih.gov/pubmed?term=Storniolo%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Rugo HS (http://www.ncbi.nlm.nih.gov/pubmed?term=Rugo%20HS%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Sledge G (http://www.ncbi.nlm.nih.gov/pubmed?term=Sledge%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Aktan G (http://www.ncbi.nlm.nih.gov/pubmed?term=Aktan%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Ellis C (http://www.ncbi.nlm.nih.gov/pubmed?term=Ellis%20C%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Florance A (http://www.ncbi.nlm.nih.gov/pubmed?term=Florance%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Vukelja S (http://www.ncbi.nlm.nih.gov/pubmed?term=Vukelja%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Bischoff J (http://www.ncbi.nlm.nih.gov/pubmed?term=Bischoff%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), Baselga J (http://www.ncbi.nlm.nih.gov/pubmed?term=Baselga%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807), O'Shaughnessy J (http://www.ncbi.nlm.nih.gov/pubmed?term=O%27Shaughnessy%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22689807).
Source
Department of Medicine/Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA. black034@mc.duke.edu
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.