VERZENIO (abemaciclib) is a targeted CDK4/6 inhibitor, delivered in the form of an oral tablet, distinct from chemotherapy. It operates within the cells, inhibiting CDK4/6 activity, and effectively restraining cancer cell growth, potentially leading to their demise. The NCCN recommends a Category 1 treatment option of 2 years of abemaciclib in combination with endocrine therapy in the adjuvant setting.

In its initial 2021 approval for adjuvant therapy, the FDA imposed a somewhat surprising requirement for a minimum 20% Ki-67 score, despite the CDK4/6 inhibitor demonstrating its capacity to reduce the risk of invasive cancer recurrence or mortality within a broader patient population. However, following its more recent 2023 approval for adjuvant breast cancer treatment, Eli Lilly's VERZENIO no longer necessitates biomarker test results for certain early breast cancer patients. It can now be employed for addressing metastatic disease without regard to menopausal status.

According to the findings presented at ESMO 2023, in the ITT population, with a median follow-up of 54 months, the addition of abemaciclib to endocrine therapy demonstrated sustained benefits in invasive disease-free survival (IDFS). The risk of invasive disease was reduced by 32%, with 407 events in the abemaciclib group compared to 585 in the endocrine therapy alone group, resulting in 5-year IDFS rates of 83.6% and 76.0%, respectively. Similarly, in the ITT population, distant recurrence-free survival (DRFS) also showed continued benefits with abemaciclib, reducing the risk of distant relapse by 32.5%. The 5-year DRFS rates were 86.0% and 79.2%, respectively. The Kaplan Meier curves maintained separation for both IDFS and DRFS, leading to 5-year absolute improvements of 7.6% and 6.7%, respectively. No new safety concerns emerged. While overall survival (OS) data were still immature, there were fewer reported deaths in the abemaciclib group compared to the placebo group, though this difference was not statistically significant.

 

VERZENIO exhibits a remarkable nearly twofold increase in progression-free survival when compared to endocrine therapy alone, signifying a substantial advancement. The monarchE trial stands as a unique adjuvant CDK4/6 inhibitor study, dedicated to high-risk patients. The ultimate aim of optimal adjuvant therapy is to eliminate micrometastatic disease within a feasible timeframe to enhance treatment compliance. 

VERZENIO has been making significant strides in the market, particularly in the post-surgery adjuvant context, distinguishing itself among the three approved CDK4/6 inhibitors. In the United States , the estimated market size of VERZENIO is expected to reach approximately USD 1.8 billion in adjuvant HR+/HER2-negative setting only.

KOL insights

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to ET for patients with HR-positive, HER2-negative, node-positive, high-risk early breast cancer”– MD, PhD, director of the Breast Center, Germany.

“The mature recurrence efficacy benefit demonstrated in monarchE, achieved with a 2-year treatment duration, reinforce abemaciclib as the standard of care in this curative setting, where abemaciclib is the only CDK4/6 inhibitor approved to treat people with HR-positive, HER2-negative, node-positive, high-risk early breast cancer”–MD, chief medical officer.

Conclusion

In patients with early breast cancer (EBC) and lymph node involvement, there is a significant risk of cancer recurrence, which can be as high as 30% within five years. The MonarchE trial stands out as the only study focused on high-risk EBC patients, aiming to enhance their treatment. Notably, at the critical 5-year milestone for adjuvant EBC trials, the combination of abemaciclib and endocrine therapy continued to substantially reduce the risk of both invasive and distant cancer recurrence, even after the completion of treatment. What's particularly noteworthy is that the benefit of abemaciclib observed in MonarchE increased over time, showing a 6.7% absolute improvement at the 5-year mark compared to the rates at 2, 3, and 4 years. Importantly, the safety profile remained consistent with prior MonarchE analyses. This escalating benefit over five years suggests a sustained impact, making a compelling case for the use of abemaciclib in high-risk EBC patients. Furthermore, there are encouraging trends in overall survival data favoring the abemaciclib treatment group, and the study's follow-up is ongoing. Abemaciclib exerts a potent and enduring effect by promoting cell death, and it differs from other CDK4/6 inhibitors, which are administered intermittently and promote cellular senescence.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to- Metastatic HR+ HER2-negative Breast Cancer Market Forecast Report