Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer.
BACKGROUND
Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer.


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.


CONCLUSIONS
The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.
Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA.
Suleiman
S
Massarweh
Jessica
J
Moss
Chi
C
Wang
Edward
E
Romond
Stacey
S
Slone
Heidi
H
Weiss
Rouzan G
RG
Karabakhtsian
Dana
D
Napier
Esther P
EP
Black
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000378:metabolism; D000077157:Sorafenib; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D009536:Niacinamide; D000077157:Sorafenib
PDGF receptor-α; Ras/Raf/MAPK; VEGF receptor 2; angiogenesis; breast cancer; endocrine resistance