KEY TAKEAWAYS
- A MonarchE phase 3 randomized trial for efficacy and safety of abemaciclib plus endocrine therapy (ET) for premenopausal patients with HR+, HER2- EBC.
- Premenopausal patients with HR+ and HER2- tumors may have different tumor biology and treatment response than postmenopausal patients.
- Abemaciclib with ET significantly reduced the risk of developing IDFS and DRFS events, with a numerically greater effect size in premenopausal patients.
- Definite improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates.
- The choice of ET for premenopausal patients varied considerably between countries.
- Abemaciclib with ET is safe and effective for premenopausal patients with HR+, HER2- EBC, with a consistent safety profile as the overall population.
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 abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitors approved for use in various regions. Tumour biology and treatment response may vary between premenopausal and postmenopausal individuals with HR+ and HER2- malignancies. For the substantial subgroup of premenopausal patients with HR+, HER2- EBC in monarchE, they explain the efficacy and safety of abemaciclib combined endocrine therapy (ET).
Patients randomly assigned to undergo adjuvant ET with or without abemaciclib did so for 2 years, with at least 3 more years of ET given if clinically necessary. Patients were divided into premenopausal and postmenopausal groups based on their menstrual status at the time of diagnosis. The treating physician combined standard ET (tamoxifen or aromatase inhibitor) with a gonadotropin-releasing hormone agonist. The data cutoff was 1 April 2021, and invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) were analyzed in a menopausal state (median follow-up of 27 months).
Patients assigned to receive hormone replacement therapy included 3,181 (56.4%) postmenopausal and 2,451 (43.5%) who had not yet reached menopause. Premenopausal women’s options for ET varied widely between countries. Therapy benefited patients regardless of menopausal status, while the premenopausal group saw a more significant effect size. Abemaciclib plus ET reduced the probability of IDFS and DRFS occurrences by 42.2% and 40.3%, respectively, in premenopausal patients.
In 3 years, the IDFS rate was up 5.7%, while the DRFS rate was up 4.4%. The overall safety profile was maintained in premenopausal patients. Regardless of menopausal state or prior ET, adding abemaciclib improved IDFS and DRFS compared to the et al. one. The improvement was statistically more significant in the premenopausal than in the postmenopausal population. Abemaciclib’s safety statistics in premenopausal patients align with the drug’s safety profile.
Source: https://pubmed.ncbi.nlm.nih.gov/36756142/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03155997/
Paluch-Shimon, S., Neven, P., Huober, J., Cicin, I., Goetz, M.P., Shimizu, C., Huang, C.-S., Lueck, H.J., Beith, J., Tokunaga, E., Contreras, J.R., de Sant’Ana, R.O., Wei, R., Shahir, A., Nabinger, S.C., Forrester, T., Johnston, S.R.D. and Harbeck, N. (2023). 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. Therapeutic Advances in Medical Oncology, 15, p.175883592311518. doi:https://doi.org/10.1177/17588359231151840.
