Considerations for the Use of Abemaciclib vs Ribociclib in Breast Cancer

Both abemaciclib (Verzenio; Lilly) and ribociclib (Kisqali; Novartis) have adverse effects as well as benefits in cancer treatment, necessitating clear communication between providers and patients when deciding on a treatment regimen, according to investigators of a review article published in Therapeutic Advances in Medical Oncology.¹

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A team of researchers from Canada addressed newer treatment options for adult patients diagnosed with early hormone-receptor-positive and human epidermal growth factor receptor 2-negative breast cancer (HR+, HER2− EBC) in the recent review article. The basis for the review article was 4 trials: PALLAS, PENELOPE-B, monarchE, and NATALEE.¹

Palbociclib (Ibrance; Pfizer) plus endocrine therapy was as efficacious as endocrine therapy alone in 2 of these trials (PALLAS and PENELOPE-B). In the other 2 trials, the new CDK4/6 inhibitor was superior. Abemaciclib and ribociclib are 2 new CDK4/6 inhibitors to prevent breast cancer reoccurrence after treatment.²

The monarchE trial compared endocrine therapy with abemaciclib 150 mg orally twice a day for 2 years in comparison with endocrine therapy alone. When combined with endocrine therapy, monarchE found that abemaciclib demonstrated a significant improvement in invasive disease-free survival (IDFS) among patients with HR+, HER2- node-positive EBC at high risk of early recurrence.³

The 3-year NATALEE trial compared endocrine therapy with ribociclib versus endocrine therapy alone. Patients took a nonsteroidal aromatase inhibitor daily. Ribociclib 400 mg was taken daily for 3 weeks, and the patients skipped ribociclib for 7 days. This dosing schedule was repeated every 4 weeks. Endocrine therapy was either letrozole 2.5 mg per day or anastrozole 1 mg per day for 5 or more years. Both are nonsteroidal aromatase inhibitors (NSAI). Ribociclib plus the NSAI improved IDFS in this trial.⁴

Researchers observed that abemaciclib with endocrine therapy gave 84% of patients diarrhea, 46% of patients neutropenia, and 41% of patients fatigue.¹ Among patients with endocrine therapy alone, 38% had arthralgia, 23% had hot flushes, and 18% were fatigued. Although those numbers appear high, severity varied.¹

Abemaciclib severely lowered all white blood cells at a frequency of 11% and neutrophils specifically at a rate of 20% during the monarchE trial.¹ Additionally, abemaciclib caused severe diarrhea in 8% of patients.¹

Ribociclib resulted in severe neutropenia among 44% of patients and severely raised liver enzymes in 9% of patients.² A majority of patients (62%) who took ribociclib with NSAI had severe adverse effects compared with 18% of patients who did not take ribociclib.¹

Ribociclib raises the chance of QTc prolongation.¹ Patients must have an electrocardiogram before starting ribociclib and 2 weeks after initiation. Patients with inflammatory bowel disease should avoid abemaciclib.¹

Patients who took abemaciclib plus endocrine therapy had a 6% lower mortality after 4 years and 7.6% lower mortality after 5 years compared to those who used endocrine therapy alone.¹

Meanwhile, ribociclib plus NSAI only provided a 4.9% improvement after 4 years. Population risk level and survival end points were different in the trials. The patient age range in the trials was 23 to 89 for abemaciclib and 24 to 90 for ribociclib.¹

The emergence of abemaciclib and ribociclib, while representing significant advancements in the treatment of HR+, HER2-negative breast cancer, introduces a new layer of complexity for oncology pharmacists. The distinct adverse effect profiles of these CDK4/6 inhibitors, particularly the higher rates of diarrhea and neutropenia observed with abemaciclib and the potential for QTc prolongation with ribociclib, necessitate meticulous monitoring and proactive patient education. Oncology pharmacists are therefore critical in ensuring safe and effective implementation of these therapies by vigilantly assessing patients for contraindications, managing potential drug interactions, and providing comprehensive counseling on adverse event management and adherence. Their expertise in navigating these nuances will be paramount in optimizing patient outcomes and integrating these valuable treatment options into clinical practice.

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;17. doi:10.1177/17588359251326710

2. Conner K. What Are CDK4/6 Inhibitors? Breastcancer.org. Updated January 13, 2025. Accessed May 8, 2025. https://www.breastcancer.org/treatment/targeted-therapy/what-are-cdk46-inhibitors

3. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. doi:10.1200/JCO.20.02514

4. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390:1080-1091. doi:10.1056/NEJMoa2305488