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 the background of the ELAINE-1 study (NCT03781063) examining lasofoxifene in patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer harboring estrogen receptor 1 (ESR1) mutations.

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.

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0:08 | A major question for the field and for these ESR1 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 ESR1 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 ESR1 mutations?

0:48 | 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.

1:07 | 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 ESR1 mutations. With that in mind, the ELAINE-1 trial is testing whether lasofoxifene would be superior to fulvestrant for the treatment of ESR1-mutated metastatic breast cancer.