ELAINE 3: phase 3 study of lasofoxifene plus abemaciclib to treat ER+/HER2-, <i>ESR1</i> -mutated, metastatic breast cancer

Endocrine therapy (ET) is recommended for patients with estrogen receptor-positive (ER+) metastatic breast cancer (mBC), but most patients will develop treatment resistance, often due to mutations in the ER-α-coding gene, <i>ESR1</i>. Therapeutic options are limited for endocrine-resistant mBC, particularly following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Lasofoxifene had anti-tumor activity in two separate phase 2, open-label studies (ELAINE 1 and 2) when given as monotherapy or combined with abemaciclib. The phase 3, randomized ELAINE 3 trial will evaluate the efficacy and safety of lasofoxifene/abemaciclib versus fulvestrant/abemaciclib for locally advanced or metastatic, ER+/HER2- breast cancer with an <i>ESR1</i> mutation that progressed after ET-CDK4/6i treatment. Enrollment is planned for up to 500 patients to evaluate progression-free survival as the primary endpoint.<b>Clinical trial registration:</b> www.clinicaltrials.gov identifier is NCT05696626.