Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2-, node-positive, high-risk early breast cancer.

Abstract

Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2- tumors may have different tumor biology and treatment response compared to postmenopausal patients. We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2- EBC in monarchE. Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated. Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician's choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months). Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population. Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.