Selection Considerations for Abemaciclib Versus Ribociclib in Early HR+/HER2- Breast Cancer: Efficacy, Safety, and Long-Term Outcomes

Two new treatments are changing the landscape for some patients with breast cancer: abemaciclib and ribociclib. In recent research, a team of researchers from Canada addressed these newer treatment options for adult patients diagnosed with early hormone-receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer in a review article published in Therapeutic Advances in Medical Oncology.¹

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The basis for the review article was 4 clinical trials: PALLAS, PENELOPE-B, monarchE, and NATALEE. Palbociclib plus endocrine therapy was equally as efficacious as endocrine therapy alone in PALLAS and PENELOPE-B, so the remaining 2 trials were the primary focus of the article. The patient age range in the trials was 23 to 89 for abemaciclib and 24 to 90 for ribociclib.¹

Abemaciclib and ribociclib are 2 new CDK4/6 inhibitors indicated to prevent breast cancer recurrence after treatment.¹Trial participants received a CDK4/6 inhibitor in combination with adjuvant endocrine therapy such as tamoxifen or an aromatase inhibitor.² Patients received abemaciclib 150 mg twice a day with endocrine therapy in the monarchE trial, whereas patients enrolled in the NATALEE trial received non-steroidal aromatase inhibitors (NSAI) and ribociclib 400 mg once daily for 3 weeks, then paused taking medication for 1 week.¹

Researchers observed that abemaciclib with endocrine therapy caused diarrhea in 84% of patients, neutropenia in 46% of patients, and fatigue in 41% of patients.¹ Among those who received only endocrine therapy, 38% of patients experienced arthralgia, 23% experienced hot flushes, and 18% were fatigued, all to varying degrees.¹

Abemaciclib alone severely lowered all white blood cell counts at a frequency of 11% and neutrophils at a rate of 20% and resulted in severe diarrhea among 8% of participants in the monarchE trial.¹ Meanwhile, ribociclib resulted in severe neutropenia among 44% of patients and severely raised liver enzymes in 9% of patients.¹ A majority of patients (62%) who received ribociclib with an NSAI experienced severe adverse effects compared with just 18% of patients who received an NSAI medication alone.¹

Finally, patients who received abemaciclib plus endocrine therapy had a 6% lower mortality after 4 years and a 7.6% lower mortality after 5 years than those who received endocrine therapy alone.¹

Ribociclib plus NSAI only provided a 4.9% improvement after 4 years. Population risk level and survival end points were different in the 2 trials.¹

Selecting between abemaciclib and ribociclib in early HR-positive, HER2-negative breast cancer requires careful consideration of trial evidence, toxicity profiles, and patient-specific factors. Abemaciclib offers a modestly greater survival benefit over ribociclib but carries a higher risk of gastrointestinal adverse effects, whereas ribociclib is associated with more hematologic and hepatic toxicities. The differences in study populations, treatment regimens, and end points underscore the importance of shared decision-making between oncologists and patients to tailor therapy to clinical needs, comorbidities, and patient preferences.

REFERENCES

1. Hussain M, Brezden-Masley C, Chia S, Curigliano G, Webster M, Henning JW. Clinician’s guide: expert insights on the use of CDK4/6 inhibitors in patients with early breast cancer. Ther Adv Med Oncol. 2025. doi:10.1177/17588359251326710

2. Rao RD, Cobleigh MA. Adjuvant endocrine therapy for breast cancer. Oncology (Williston Park). 2012;26(6):541-547.