121IN - Putting drugs at work against brain metastases in HER2 positive BC: Results of the Landscape trial

Date 29 September 2012
Event ESMO Congress 2012
Session ESMO-ESTRO Joint symposium: Innovative approaches to the treatment of brain metastases
Topics Anticancer agents
Central Nervous System Malignancies
Therapy
Biological Therapy
Presenter Thomas Bachelot
Authors T. Bachelot1, G. Romieu2, C. Cropet3, M. Campone4, V. Dieras5, M. Jimenez6, F. Dalenc7, E. Le Rhun8, C. Labbe-Devilliers4
  • 1Centre Léon Bérard, 69008 - Lyon/FR
  • 2Oncologie Médicale, Centre Val d'Aurelle, Montpellier/FR
  • 3Unité De Biostatistique Et D'evaluation Des Thérapeutiques, Centre Léon Bérard, 69008 - Lyon/FR
  • 4Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de l'Ouest, 44805 - St Herblain/FR
  • 5Department Of Medical Oncology, Clinical Trial Unit, Institut Curie, 75005 - Paris/FR
  • 6R&d, Unicancer, 75013 - Paris/FR
  • 7Oncologie Médicale, Centre Claudius Regaud, Toulouse/FR
  • 8Département De Sénologie, Centre Oscar LAMBRET, 59000 - Lille/FR

Abstract

Background

Brain metastases (BM) occur in 30 to 50% of metastatic breast cancers (MBC) overexpressing HER2. In case of diffuse BM, current treatment is primarily based on whole brain radiotherapy (WBRT). Few systemic options are available. Lapatinib (L) has shown some activity in association with capecitabine (C) after previous WBRT. The LANDSCAPE study assessed the efficacy of the association before any local treatment.

Methods

Eligible pts had HER2+ MBC with BM not previously treated with WBRT, C or L. They received lapatinib 1,250 mg once daily and oral capecitabine 2,000 mg/m2 from day 1 to day 14, every 21 days. The primary endpoint was the rate of central nervous system objective responses (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of all the following: increasing steroid use, progressive neurologic symptoms, or progressive extra-CNS disease. Secondary endpoints included time to progression (TTP), time to WBRT, and toxicity.

Findings

From April 2009 to August 2010, forty-five patients were included in the study. 44 patients were evaluable for efficacy, with a median follow-up of 21.2 months (range 2.2-27.6).The CNS-OR rate was 67.4% (95% CI: 51.5%-80.9%). Thirty-seven patients (86%) exhibited a reduction in tumor volume. Median time to progression was 5.5 months (95% CI: 4.3-6). At the time of analysis, 81.8% of patients had received brain radiotherapy, median time to radiotherapy was 8.3 months (95% CI: 5.4-9.1). Most adverse events (AE) were grade 1-2 as already reported for this association, 22 patients (49%) experienced grade 3 or 4 treatment related toxicity and 14 patients presented at least one SAE; treatment was discontinued due to toxicity in 4 pts

Interpretation

The association of L and C is effective in the treatment of BM of HER2 positive BC. Our data suggest that this regimen might be used right away at diagnosis of BM. This approach might change the management of selected patients with BM, allowing a delayed WBRT. This strategy deserves further evaluation to confirm the clinical benefits for patients in terms of survival, cognitive functions and quality of life. We are currently planning such a randomized clinical trial.

Disclosure

T. Bachelot: GSK: Board member Travel accommodation Reaserch grant,

M. Campone: GSK: Board Member,

V. Diéras: GSK: Board Member.

All other authors have declared no conflicts of interest.