Verzenio (abemaciclib)

Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences.

Mifepristone provided marked palliative benefit in this patient with nPR-negative, metastatic breast cancer, suggesting potential therapeutic value in similar cases. Confirmation of efficacy will require larger studies focused on tumors with absent or minimal nuclear progesterone receptor expression.

P1, N=17, Recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2026 --> Sep 2027 | Trial primary completion date: Dec 2025 --> Jan 2027

P1, N=8, Completed, OHSU Knight Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jun 2025

P1, N=396, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Jun 2027

P2, N=28, Recruiting, The Methodist Hospital Research Institute | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib. In this article, we focus on heterogeneous vulnerabilities of cancers as consequences of various genetic and epigenetic alterations in the cell cycle-regulatory network, and we discuss how next-generation cell-cycle-targeting drugs currently in the developmental pipeline could exploit these heterogeneous vulnerabilities in the cancer cell cycle. We hope to provide a forward-looking perspective on directions for therapeutic cell-cycle targeting in the advent of personalized precision medicine.

To explore this, we developed palbociclib- (2PR, 9PR, TPR) and abemaciclib- (2AR, 9AR, TAR) resistant ER+ breast cancer sublines through prolonged drug exposure over six months. Additionally, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) was strongly upregulated in palbociclib-resistant cells. Together, these findings identify a distinct, non-canonical senescence phenotype associated with CDK4/6i resistance and may provide a foundation for identifying new vulnerabilities in resistant ER+ breast cancers through targeting SASP-related signaling.

Simulations using the combined pharmacokinetic-tumor size-time to event model demonstrated the adequacy of a 150 mg twice daily dose in combination with fulvestrant. There was a negligible impact of dose reductions on efficacy, likely due to the shallow exposure-response relationship. When analyzing survival data where the drug exposure changes significantly within an individual over time, it is important to maximize the use of available longitudinal data through simultaneous modeling of time-course tumor size and survival data.

P1, N=198, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026

Real-world safety, tolerability, and effectiveness of abemaciclib in Chinese patients with HR+/HER2- EBC and ABC were consistent with clinical trials, with no new safety signals, supporting its positive real-world benefit-risk profile.