CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00653
Objective:Brain metastases occur in 3050% of patients with metastatic human epidermal growth factor receptor 2positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. They aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from human epidermal growth factor receptor 2positive breast cancer.
Authors:Bachelot T, et al
Title:Lapatinib plus capecitabine in patients with previously untreated brain metastases from human epidermal growth factor receptor 2positive metastatic breast cancer (LANDSCAPE): a singlegroupphase 2 study.
Journal:Lancet Oncol.
Year:2013
PMID:23122784
Trial Design
Clinical Trial Id:NCT00967031
Agent:lapatinib
Target:Epidermal growth factor receptor
Receptor proteintyrosine kinase erbB2
Cancer Type:advanced cancer with brain metastasis
Cancer Subtype:brain metastases from human epidermal growth factor receptor 2-positive breast cancerhuman epidermal growth factor receptor 2positive breast cancer
Therapy Type:com
Therapeutic Combination Type:2
Therapeutic Combination Content:Lapatinib plus capecitabine
Study Type:singlearmphase II, openlabel, multicentre study
Key Patients Feature:Patientsaged 18 years or older were eligible if they hadhistologically confirmed metastatic breast cancer withoverexpression of human epidermal growth factor receptor 2, defined as 3+ byimmunohistochemistry or 2+ and evidence of geneamplification by fl uorescence insitu hybridisation; atleast one measurable CNS lesion of 10 mm or greater indiameter on MRI; Eastern Cooperative Oncology Group(ECOG) performance status of 0 to 2; and adequatehaematological, renal, and hepatic function as assessedby blood tests. Any previous systemic treatment of breastcancer, except with lapatinib or capecitabine, was allowed.
Biomarker:human epidermal growth factor receptor 2positive
Biomark Analysis:NA
Control Group Info:single arm
Treatment Info:Tretament was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m(2), orally) from day 1 to day 14.
Primary End Point:the proportion of patients with an objective CNS response, progressive neurological symptoms, and progressive extraCNS disease.
Secondary End Point:NA
Patients Number:45
Trial Results
DLT_MTD:NA
Objective Response Rate:29 patients had an objective CNS response (65.9%, 95% CI 50.179.5); all were partial responses.
Disease Control Rate:NA
Median Time to Progression:5.5 months (95% CI 4.3-6.0)
Median PFS A vs. C:NA
Median OS A vs. C:17.0 months (13.7-24.9)
Adverse Event(agent arm): Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatmentrelated adverse events, of which the most common were diarrhoea in nine (20%) patients and handfoot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred.
Conclusions:The combination of lapatinib and capecitabine is active as firstline treatment of brain metastases from human epidermal growth factor receptor 2positive breast cancer. Aphase 3 trial is warranted.