Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer

Suleiman Massarweh, Jessica Moss, Chi Wang, Edward Romond, Stacey Slone, Heidi Weiss, Rouzan G. Karabakhtsian, Dana Napier, Esther P. Black

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer.

Materials & methods: A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by RECIST after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual.

Results: Eight out of 11 patients had progressive disease on study entry and three had stable disease. Of the ten evaluable patients, seven experienced stable disease (70%) and three experienced progressive diseas (30%), with a median time to progression of 6.1 months (8.4 months in the seven patients on tamoxifen). The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor-α. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways.

Conclusion: The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.

Original languageEnglish (US)
Pages (from-to)2435-2448
Number of pages14
JournalFuture Oncology
Volume10
Issue number15
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

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Keywords

  • PDGF receptor-α
  • Ras/Raf/MAPK
  • VEGF receptor 2
  • angiogenesis
  • breast cancer
  • endocrine resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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