Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+ HER2− Early Breast Cancer

Abstract

Objective: To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. Data Sources: A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. Study Selection and Data Extraction: Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. Data Synthesis: Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. Relevance to Patient Care and Clinical Practice: This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2− EBC at high risk for recurrence. Conclusion: Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2− node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway

“…CDK4/6 inhibitors, including Palbociclib [ 276 , 277 ], ribociclib [ 278 , 279 ], and abemaciclib [ 280 , 281 ], have demonstrated notable effectiveness in HR+ BC. These inhibitors work by targeting CDK4/6, inducing cell cycle arrest and suppressing tumor cell proliferation.…”

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

“…Among these, abemaciclib is the first US Food and Drug Administration (FDA)-approved CDK4/6 inhibitor for adjuvant therapy in HR + HER2 − early-stage breast cancer. 42 PI3K/Akt/mTOR pathway The phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is frequently activated in response to various extracellular stimuli, such as growth factors, hormones, and cytokines. [43][44][45] PI3K is mainly triggered by the two largest groups of membrane receptors: receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs).…”

CDK Inhibitors and FDA: Approved and Orphan

“…An additional requirement was having a Ki-67 score of greater than or equal to 20%. This approval was based on the monarchE trial [31,32]. On 3 March 2023, the FDA approved abemaciclib with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node- Ribociclib (LEE011, KISQALI) (Figure 1) has slightly greater potency against cyclin D1/CDK4 (IC50 = 10 nM) than against cyclin D1, 2, 3/CDK6 (IC50 = 39 nM), but almost none against other CDKs (IC50 > 50,000) [21].…”

“…An additional requirement was having a Ki-67 score of greater than or equal to 20%. This approval was based on the monarchE trial [31,32]. On 3 March 2023, the FDA approved abemaciclib with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive early breast cancer at a high risk of recurrence.…”