Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

Sarah Sammons, Noah Kornblum, Kimberly L. Blackwell

Research output: Contribution to journalArticle

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Abstract

Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy. As most patients in this setting have already developed mechanisms of resistance to endocrine therapy, targeting biological pathways associated with endocrine resistance in combination with fulvestrant may improve outcomes. Therefore, evidence supporting a combinatorial treatment approach in the second-line setting was investigated based on a search of PubMed and ClinicalTrials.gov. Twenty-eight studies of targeted therapies plus fulvestrant as second-line treatment for HR+ ABC were identified, including three and six key randomized trials exploring cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors plus fulvestrant respectively. Additional combinations with fulvestrant included inhibitors of epidermal growth factor receptors, androgen receptor, and the bromodomain and extra-terminal family of proteins. Across the studies reviewed with available data, the addition of targeted therapies to fulvestrant resulted in clinically meaningful improvements in progression-free survival compared with fulvestrant alone. While some challenging toxicities were observed, most adverse events could be effectively managed. Selection of second-line targeted therapy for use with fulvestrant should consider prior treatment as well as the mutation status of the tumor. In conclusion, available data indicate that fulvestrant combined with agents targeting mechanisms of endocrine resistance is a promising approach. The ongoing trials identified in this review will help further inform the selection of combination treatments with fulvestrant for HR+ ABC.

Original languageEnglish (US)
JournalTargeted Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Hormones
Breast Neoplasms
Therapeutics
Cyclin-Dependent Kinase 6
fulvestrant
Cyclin-Dependent Kinase 4
Phosphatidylinositol 3-Kinase
Aromatase Inhibitors
Biological Therapy
Androgen Receptors
Sirolimus
PubMed
Disease-Free Survival
Mutation
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer. / Sammons, Sarah; Kornblum, Noah; Blackwell, Kimberly L.

In: Targeted Oncology, 01.01.2018.

Research output: Contribution to journalArticle

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