Key Points
• Source: JAMA Oncology
• Meaning: “The results of this analysis of the monarchE randomized clinical trial found that treatment with adjuvant abemaciclib plus endocrine therapy demonstrated benefit for patients with hormone receptor–positive, ERBB2−, node-positive, and high-risk early breast cancer who received neoadjuvant chemotherapy before trial enrollment.”
• In the current prespecified analysis of the monarchE randomized clinical trial, abemaciclib and endocrine therapy exhibited clinically meaningful benefit in terms of invasive disease-free survival and distant relapse-free survival. The absolute improvement was 6.6% in 2-year invasive disease-free survival rates and 6.7% in 2-year distant relapse-free survival rates. Investigators noted consistent evidence of treatment benefit in residual pathological breast tumor size or the number of positive lymph nodes at surgery.
• According to biochemical and cell-based assays, abemaciclib has demonstrated a stronger inhibition of CDK4 vs CDK6 compared with that of palbociclib. This difference in mechanism allows for the continuous administration of abemaciclib.
• “In vitro studies have shown that continuous drug exposure of HR+ BC cells is required for profound inhibition of DNA synthesis, and a similar effect in patients could play a role in the sustained tumor growth inhibition of micrometastatic disease,” the authors stated. “Moreover, CDK4 has been shown to play an essential role in the development/growth of breast cancer in animal models. Also, in breast cancer cell lines, abemaciclib was a more potent inducer of senescence and apoptosis than palbociclib.”
• One limitation of the current analysis is that it was exploratory and thus not powered or controlled for suitable statistical testing. Another limitation is that complete information regarding tumor characteristics before and after prior chemotherapy was not mandated.