Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer. (December 2014)

• Record Type: Journal Article
• Authors: Massarweh, Suleiman; Moss, Jessica; Wang, Chi; Romond, Edward; Slone, Stacey; Weiss, Heidi; Karabakhtsian, Rouzan G; Napier, Dana; Black, Esther P
• Is Part Of: Future oncology. Volume 10:Number 15(2014)
• Page Start: 2435
• Page End: 2448
• Publication Date: 2014-12
• Subjects: angiogenesis -- breast cancer -- endocrine resistance -- PDGF receptor-α -- Ras/Raf/MAPK -- VEGF receptor 2; Oncology -- Periodicals; 616.99405
• DOI: 10.2217/fon.14.99
• Languages: English
• ISSNs: 1479-6694

Abstract

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.