A randomized phase II study of lapatinib pazopanib versus lapatinib in patients with HER2 inflammatory breast cancerReportar como inadecuado




A randomized phase II study of lapatinib pazopanib versus lapatinib in patients with HER2 inflammatory breast cancer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Breast Cancer Research and Treatment

, Volume 137, Issue2, pp 471482

First Online: 13 December 2012Received: 19 November 2012Accepted: 30 November 2012DOI: 10.1007-s10549-012-2369-x

Cite this article as: Cristofanilli, M., Johnston, S.R.D., Manikhas, A. et al. Breast Cancer Res Treat 2013 137: 471. doi:10.1007-s10549-012-2369-x

Abstract

This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500mg+placebo or lapatinib 1,500mg+pazopanib 800mg double-blind once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study VEG20007, Cohort 1 was closed. The protocol was amended such that an additional 88patients Cohort 2 were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500mg, lapatinib 1,000mg+pazopanib 400mg, or monotherapy pazopanib 800mg, respectively. The primary endpoint was overall response rate ORR. Secondary endpoints included duration of response, progression-free survival PFS, overall survival, and safety. In Cohort 1, ORR for the lapatinib n=38 and combination n=38 arms was 29 and 45%, respectively; median PFS was 16.1 and 14.3weeks, respectively. Grade 3 adverse events AEs were more frequent in the combination arm 71% than in the lapatinib arm 24%. Dose reductions and interruptions due to AEs were also more frequent in the combination arm 45 and 53%, respectively than in the lapatinib monotherapy arm 0 and 11%, respectively. In Cohort 2, ORR for patients treated with lapatinib n=36, lapatinib+pazopanib n=38, and pazopanib n=13 was 47, 58, and 31%, respectively; median PFS was 16.0, 16.0, and 11.4weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade 3 AEs were reported for 17, 50, and 46% of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23%, respectively. The lapatinibpazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population.

KeywordsLapatinibPazopanibInflammatory breast cancerHER2-positive breast cancerPreviously presented at the 48th Annual Meeting of the American Society of Clinical Oncology, June 15, 2012, Chicago, IL.

This study is reported on behalf of VEG108838 Study Investigators. A complete list of the members of the VEG108838 Study Investigators appears in the -Appendix-.

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Autor: MassimoCristofanilli - StephenR.D.Johnston - AlexeyManikhas - HenryL.Gomez - OlegGladkov - ZhiminShao - SufiaSafina - KimberlyL.Bl

Fuente: https://link.springer.com/







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