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 Citations (Scopus)

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
StatePublished - Dec 1 2014
Externally publishedYes

Fingerprint

Estrogen Receptors
Breast Neoplasms
Encyclopedias
Genes
Platelet-Derived Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
Tamoxifen
Therapeutics
Microarray Analysis
Intercellular Signaling Peptides and Proteins
Biomarkers
Genome
Safety
Survival
sorafenib
Serum

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer. / Massarweh, Suleiman; Moss, Jessica; Wang, Chi; Romond, Edward; Slone, Stacey; Weiss, Heidi; Karabakhtsian, Rouzan G.; Napier, Dana; Black, Esther P.

In: Future Oncology, Vol. 10, No. 15, 01.12.2014, p. 2435-2448.

Research output: Contribution to journalArticle

Massarweh, Suleiman ; Moss, Jessica ; Wang, Chi ; Romond, Edward ; Slone, Stacey ; Weiss, Heidi ; Karabakhtsian, Rouzan G. ; Napier, Dana ; Black, Esther P. / Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer. In: Future Oncology. 2014 ; Vol. 10, No. 15. pp. 2435-2448.
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