Matthew Goetz, MD

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the background of the ELAINE-1 study (NCT03781063) examining lasofoxifene in patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer harboring 

In ELAINE 1, investigators sought to evaluate the safety and efficacy of lasofoxifene vs fulvestrant (Faslodex) through looking at the primary end point of progression-free survival and secondary end points of overall response rate, clinical benefit rate, overall survival, and safety.

Patients were randomized to receive oral lasofoxifene 5 mg and fulvestrant 500 mg as an intramuscular injection on days 1, 15, and 29, then every 4 weeks thereafter. Treatment continued until progression, death, unacceptable toxicity, or withdrawal.

A major question for the field and for these 

 mutations is how best to target them. In the setting of PALOMA-3 [NCT01942135], the addition of a CDK4/6 inhibitor to fulvestrant improved outcome in patients that had these 

 mutations. CDK4/6 inhibitors are clearly an advance. The remaining question that comes up is, what's the best endocrine therapy that should be used to target these 

We've thought for quite some time that fulvestrant would be the best drug based on both preclinical and early clinical data. We have data with the oral selective estrogen receptor down regulators [SERDS] and these have clearly demonstrated a signal of benefit preclinically as well as clinically.

That leads us to a new drug called lasofoxifene in a new class, meaning being tested in 2022, but not a new class overall as SERMs have been around for quite some time. Lasofoxifene is an older drug that was tested years ago and has shown to be an effective drug for the prevention of breast cancer. In the last 5 years, it's been tested in preclinical models and demonstrated that this drug effectively targets and inhibits the growth and metastases of ER-positive or HER2-negative breast cancer models that contain 

 mutations. With that in mind, the ELAINE-1 trial is testing whether lasofoxifene would be superior to fulvestrant for the treatment of 

Videos

Matthew P. Goetz, MD, discusses the background of the ELAINE-1 study examining lasofoxifene in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer harboring estrogen receptor 1 mutations.


ELAINE-1 Trial Examines Lasofoxifene in ESR1+, ER+/HER2- Breast Cancer

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses recent data on estrogen receptor (ER) mutations in patients with breast cancer.

According to Goetz, ER mutations are fairly new when examining hormonal therapy. During the 2022 European Society for Medical Oncology (ESMO) Congress, Goetz highlighted research on ER mutations by providing the results of the ELAINE 1 trial (NCT03781063).

ELAINE 1 evaluated the safety and efficacy of lasofoxifene vs fulvestrant (Faslodex) in patients with locally advanced/metastatic breast cancer and an estrogen receptor 1 mutation who progressed on aromatase and CDK 4/6 inhibitors.

 Estrogen receptor mutations are something that's relatively new in terms of the study of hormonal therapy. It's been thought for some time that these mutations might be present and indeed, the work done 20-30 years ago, when people looked at this, found that these mutations are very rare in the primary tumor, but they do occur and are selected, if you will, in the setting of ongoing hormonal therapy, in particular, aromatase inhibitors.

These mutations confer ligand-independence. That means that the receptors constituently active, it signals and can induce the effects of what what otherwise would occur in the presence of the ligand, and that is the estrogen. One of the things that we know is that these mutations are a major driver of resistance to aromatase inhibitors. They occur fairly frequently, up to 30%-40% of the time in the metastatic setting.

We also have emerging data that these mutations tend to confer a worse prognosis, especially those that have multiple mutations. This worse prognosis is clinically associated with higher rates of metastases. Certainly, therapeutic resistance, presents of visceral disease, and again, worse overall survival.

Matthew P. Goetz, MD, discusses recent data on estrogen receptor mutations in patients with breast cancer.


Examining Estrogen Receptor Mutations in ER+/HER2- Breast Cancer

Matthew Goetz, MD, professor of oncology and pharmacology, Mayo Clinic, discusses a secondary analysis of the MONARCH 1 and MONARCH 2 clinical trials in breast cancer.

Matthew Goetz, MD | Authors

Articles

ELAINE-1 Trial Examines Lasofoxifene in ESR1+, ER+/HER2- Breast Cancer

Examining Estrogen Receptor Mutations in ER+/HER2- Breast Cancer

Dr. Goetz Discusses a Secondary Analysis of the MONARCH Trials in Breast Cancer