Verzenio Offers Potential Benefit After Prior Therapy in HR+/HER2– Breast Cancer

Data from the retrospective rAMBER study, presented at the 2025 San Antonio Breast Cancer Symposium(SABCS), showed that Verzenio (abemaciclib) monotherapy offered clinical benefit to some patients with hormone receptor (HR)–positive, HER2-negative breast cancer who had progressed on prior CDK4/6 inhibitor therapy.

The study evaluated how effective Verzenio could be when used alone after progression on previous CDK4/6 therapy, offering insight into the potential of sequential treatment in this patient population.

Approximately 33% of patients who received Verzenio across four academic centers (30 patients) derived meaningful clinical benefit from the therapy. Verzenio was generally well tolerated for more than 180 days, even in patients whose disease had progressed on prior Ibrance therapy and ongoing endocrine treatments. Most patients (23 of 30) continued on Verzenio until either disease progression or death, while the remaining 7 patients discontinued therapy due to side effects.

The median duration of treatment with Verzenio was 4 months following progression on Ibrance-based therapy, and the median number of intervening lines of therapy between Ibrance and Verzenio was 2, highlighting the potential of Verzenio to offer disease control even after multiple prior treatments.

“CDK4/6 inhibitors have become the standard of care for patients with advanced HR-positive, HER2-negative breast cancer. However, uncertainty remains regarding the efficacy of re-introducing CDK4/6 inhibitors after disease progression on prior therapy,” said Dr. Sahar Shahamatdar, an internal medicine resident at Massachusetts General Hospital, and her coauthors. “rAMBER is the first study to evaluate the effectiveness of Verzenio monotherapy in this setting, offering new insights into sequential CDK4/6 therapy and potential treatment strategies for patients who have exhausted standard options.”

Verzenio was approved by the U.S. Food and Drug Administration (FDA) in February 2018 for use in combination with an aromatase inhibitor as a frontline therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. This decision was supported by prior phase 3 MONARCH 3 data showing a median progression-free survival of 28.2 months with Verzenio versus 14.8 months for patients receiving placebo, confirming its efficacy in first-line settings.

The rAMBER study collected retrospective patient data from Massachusetts General Hospital, Barnes-Jewish Hospital, University of Pittsburgh Medical Center, and Moffitt Cancer Center. Patients with metastatic HR-positive, HER2-negative breast cancer who received Verzenio monotherapy after disease progression on a CDK4/6 inhibitor–based regimen were included. Patients were divided into two subgroups: sequential CDK4/6 therapy (6 patients) and nonsequential therapy (24 patients). Data were collected under Institutional Review Board–approved protocols, examining patient demographics, clinical outcomes, and treatment duration. Serial RECIST measurements were collected from imaging studies, and solid tumor and cell-free DNA were analyzed using targeted sequencing.

Each biopsy was assigned a phenotype based on the best clinical response and duration of response relative to biopsy timing, defined as sensitive, acquired resistant, or intrinsically resistant. One patient achieved a partial response with Verzenio, seven patients experienced stable disease, and eight experienced disease progression. Genomic analysis of 23 biopsies showed RB1 alterations were associated with acquired or intrinsic resistance, and 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 concluded. These findings highlight the potential of Verzenio monotherapy to provide clinical benefit even after prior CDK4/6 inhibitor therapy and demonstrate the importance of understanding tumor genetics when considering sequential treatment strategies for advanced breast cancer.

References

1. “Updated analyses from the retrospective rAMBER study exploring abemaciclib after prior CDK4/6 inhibitor progression in metastatic hormone-receptor positive breast cancer,” by Dr. Sahar Shahamatdar, et al. 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,” by the U.S. FDA. News release; Feb. 26, 2018.

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