Abemaciclib Monotherapy Shows Clinical Benefit Post-CDK4/6 Inhibitor Progression in HR+/HER2– mBC

According to data from the retrospective rAMBER study, which was presented during the 2025 San Antonio Breast Cancer Symposium, abemaciclib (Verzenio) monotherapy demonstrated a clinical benefit in a portion of patients with hormone receptor (HR)–positive, HER2-negative breast cancer following the progression of their disease on previous CDK4/6 inhibitor therapy. ¹

Approximately 33% of patients who received abemaciclib across 4 academic centers (n = 30) derived benefit from the agent. Abemaciclib was found to be tolerable for more than 180 days, despite disease progression on prior palbociclib (Ibrance) and endocrine therapies.

Most patients (n = 23 of 30) remained on abemaciclib until either disease progression or death; the remaining 7 patients discontinued therapy due to adverse effects. The median duration of treatment with abemaciclib was 4.0 months (95% CI, 2.8-13.9) following disease progression on palbociclib-based treatment. The median number of intervening lines of therapy between palbociclib and abemaciclib was 2.

“CDK4/6 inhibitors have become the standard of care for patients with advanced HR-positive, HER2-negative breast cancer. There remains uncertainty regarding the efficacy of CDK4/6 inhibitor re-introduction after progression on CDK4/6 inhibitors,” Sahar Shahamatdar, MD, PhD, an internal medicine resident physician at Massachusetts General Hospital in Boston and her coauthors wrote in a poster presentation of the data. “rAMBER is the first [study] to evaluate the effectiveness of abemaciclib monotherapy after progression on [a] CDK4/6 inhibitor, offering new perspectives on the role of sequential CDK4/6 therapies.”

In February 2018, the FDA approved abemaciclib in combination with an aromatase inhibitor for the frontline treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer.² The regulatory decision was supported by data from the phase 3 MONARCH 3 trial (NCT02246621) which showed that patients who received abemaciclib experienced a median progression-free survival of 28.2 months (95% CI, 23.5-not reached) vs 14.8 months (95% CI, 11.2-19.2) among those who received placebo (HR, 0.540; 95% CI, 0.418-0.698).

rAMBER Study Design

The study authors collected retrospective patient data at 4 academic centers: Massachusetts General Hospital, Barnes-Jewish Hospital, University of Pittsburgh Medical Center, and Moffitt Cancer Center.¹ They identified patients with metastatic HR-positive, HER2-negative breast cancer who received abemaciclib monotherapy after experiencing disease progression on CDK4/6 inhibitor–based therapy.

Patients with HR-positive metastatic breast cancer who received abemaciclib monotherapy after progression on a CDK4/6 inhibitor–based regimen were divided into 2 subgroups: those who received sequential CDK4/6 inhibitor–based therapy (n = 6) and those who received nonsequential CDK4/6 inhibitor–based therapy (n = 24).

Data were collected via Institutional Review Board–approved protocols. The study authors examined patient demographics and clinical outcomes. Serial RECIST measurements were collected from imaging studies and solid tumor and cell-free DNA were also assessed through targeted sequencing.

The study authors also performed a genomic exploration in which each biopsy was assigned a phenotype based on best clinical response and duration of response in relation to biopsy timing. Phenotypes were defined by sensitivity, acquired resistance, or intrinsic resistance.

Additional Findings

Further results from rAMBER revealed that 1 patient achieved a partial response with abemaciclib. Seven patients experienced stable disease and 8 had disease progression. Findings from a genomic analysis of 23 biopsies showed that RB1 alterations were associated with acquired or intrinsic resistance and that ESR1 alterations were found across all biopsy phenotypes.

“Preliminary genetic analyses revealed enrichment in RB1 alterations in patients with rapid disease progression,” Shahamatdar and her coauthors wrote in their conclusion.

DISCLOSURES: No disclosures were listed for Shahamatdar.

REFERENCES

1. Shahamatdar S, Clifton K, Maynard H, et al. Updated analyses from the retrospective rAMBER study exploring abemaciclib after prior CDK4/6 inhibitor progression in metastatic hormone-receptor positive breast cancer. Presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract PS1-10-01.

2. FDA approves abemaciclib as initial therapy for HR-positive, HER2-negative metastatic breast cancer. FDA. February 26, 2018. Accessed December 10, 2025. https://tinyurl.com/5xxs2bbx