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Abemaciclib (Verzenio®)

Writer: Dr. Jaimee George
Dr. Jaimee George
17h
5 min read

Drug Class: Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6)


Mechanism of Action


Abemaciclib inhibits cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), preventing them from promoting progression from G1 to S phase of the cell cycle. This can promote senescence, apoptosis, and reduced tumour size (1).


Approved Indications


  • Early breast cancer (1)

  • Advanced or metastatic breast cancer (1)

  • Mutated advanced or metastatic breast cancer (1)


Dosage and administration


  • Combination therapy with fulvestrant, tamoxifen, imlunestrant, or an aromatase inhibitor: 150 mg orally twice daily with or without food (1)

  • Monotherapy: 200 mg orally twice daily with or without food (1)


Key clinical benefits


  • Overall survival (OS)

  • Delayed disease progression

  • Delayed chemotherapy

  • Chemotherapy-free survival

  • Sustained protection against recurrence


Key clinical Studies


MONARCH 2

In the randomized Phase 3 MONARCH 2 trial, 669 premenopausal or perimenopausal women (with ovarian suppression) and postmenopausal women with hormone receptor positive, HER2 negative advanced breast cancer that had progressed during endocrine therapy were enrolled. Combination therapy with abemaciclib plus fulvestrant demonstrated a statistically significant improvement in overall survival, reaching 46.7 months compared with 37.3 months for placebo plus fulvestrant (HR 0.757; 95% CI 0.606–0.945; p=0.01). Survival benefits were particularly evident in patients with visceral disease, resistance to prior endocrine therapy, delayed disease progression, longer time to chemotherapy, and improved chemotherapy free survival (2).


An extended study found similar health-related quality of life (HRQoL), which was maintained from baseline and favorable functioning and symptoms with abemaciclib plus fulvestrant (3).


MONARCH E

In the randomized Phase 3 MONARCH E study, 5,637 patients with high risk, hormone receptor positive, HER2 negative early breast cancer underwent surgery, radiotherapy, and/or adjuvant or neoadjuvant chemotherapy. Eligible patients included those with one to four positive nodes, tumor size ≥5 cm, histologic grade 3, or centrally confirmed Ki 67 ≥20%. Participants received either endocrine therapy (ET) alone or ET in combination with abemaciclib 150 mg twice daily for two years. The primary endpoint was met, with 323 invasive disease free survival (IDFS) events showing superiority of abemaciclib plus ET (92.2%) compared with ET alone (88.7%; p=0.01; HR 0.75; 95% CI 0.60–0.93). Abemaciclib significantly improved outcomes in high risk early breast cancer patients, with a consistent safety profile (4).


At four years, mortality was similar between treatment groups, with 5.6% of patients in the abemaciclib plus endocrine therapy arm compared with 6.1% in the endocrine therapy alone arm (HR 0.929; 95% CI 0.748–1.153; p=0.50). The combination therapy group experienced higher rates of neutropenia (19.6%), leukopenia (11.4%), and diarrhoea (7.8%) compared with 0.9%, 0.4%, and 7.8%, respectively, in the endocrine therapy group. Serious adverse events occurred in 15.5% of patients receiving abemaciclib plus endocrine therapy versus 9.1% with endocrine therapy alone. Two treatment related deaths were reported in the abemaciclib arm (due to diarrhoea and pneumonitis), while none occurred in the endocrine therapy group. Overall, this study demonstrated the sustained benefits of abemaciclib after four years in patients with high risk HR+ and HER2 negative early breast cancer (5).


MONARCH 3

In the randomized Phase 3 MONARCH 3 trial, 493 women with hormone receptor positive, HER2 negative advanced breast cancer received abemaciclib in combination with a nonsteroidal aromatase inhibitor (NSAI) or NSAI with placebo as initial therapy. At a median follow up of 8.1 years, the final overall survival (OS) was 60.4% in the abemaciclib arm compared with 70.3% in the placebo arm (HR 0.804; 95% CI 0.637–1.015; p=0.0664, non significant). Median OS was 66.8 months with abemaciclib versus 53.7 months with placebo, with 65.3% versus 72.2% of OS events occurring in the respective arms. Importantly, no new safety signals were observed during long term follow up (6).


EMBER 3

In the randomized Phase 3 EMBER 3 trial, 874 patients with estrogen receptor positive, HER2 negative advanced breast cancer previously treated with aromatase inhibitors ± CDK4/6 inhibitors were enrolled. Patients received imlunestrant, standard of care (SOC; fulvestrant or exemestane), or imlunestrant in combination with abemaciclib. After a median follow up of 28.5 months, median overall survival (mOS) was 34.5 months with imlunestrant compared with 23.1 months for SOC in patients harboring an ESR1 mutation (HR 0.60; 95% CI 0.43–0.86; p=0.0043). In the overall population, mOS was not reached with imlunestrant abemaciclib versus 34.4 months with imlunestrant alone (HR 0.82; 95% CI 0.59–1.16; p=0.2622). Median progression free survival (PFS) was 10.9 months with imlunestrant abemaciclib compared with 5.5 months with imlunestrant alone (HR 0.59; 95% CI 0.47–0.74; p<0.0001), highlighting the added benefit of combination therapy (7).


Common Adverse Events


  • Diarrhea

  • Infections

  • Neutropenia

  • Fatigue

  • Abdominal pain

  • Nausea

  • Leukopeniax

  • Anemia

  • Vomiting


Contraindications

  • None (1)


Special Notes for Clinician


Clinicians should advise patients not to breastfeed during abemaciclib therapy due to potential risks in lactation. Concomitant use of ketoconazole should be avoided, and dose reductions are required when abemaciclib is administered with other CYP3A inhibitors. Similarly, concomitant use of CYP3A inducers should be avoided. Dose adjustments are necessary in patients with severe hepatic impairment. Close monitoring is recommended for neutropenia and thromboembolic events, and antidiarrheal therapy should be initiated immediately at the first sign of loose stools. Abemaciclib should be permanently discontinued in all patients who develop Grade 3 or 4 interstitial lung disease (ILD) or pneumonitis. Clinicians should also counsel patients regarding the risk of embryo fetal toxicity. In addition, abemaciclib may cause increased serum creatinine without affecting renal function; therefore, alternative measures should be used to assess renal function.



Abbreviations


CDK: cyclin-dependent kinase; HR+: hormone receptor-positive; HER2: human epidermal growth factor receptor 2; ABC: advanced breast cancer; ET: endocrine therapy; OS: overall survival; HR: hazard ratio; CI: confidence interval; NSAI: nonsteroidal aromatase inhibitor; EBC: early breast cancer; SOC: standard of care; mOS: median overall survival; ILD: Interstitial Lung Disease.


References


  1. Abemaciclib-VERZENIO® Prescribing Information. Available at https://pi.lilly.com/us/verzenio-uspi.pdf. Accessed on 04 October, 2026.


  2. Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-Negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol. 2020, 1;6(1):116-124.


  3. Kaufman PA, Toi M, Neven P, et al. Health-Related Quality of Life in MONARCH 2: Abemaciclib plus Fulvestrant in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer After Endocrine Therapy. Oncologist. 2020, 25(2):e243-e251. doi: 10.1634/theoncologist.2019-0551.


  4. Johnston SRD, Harbeck N, Hegg R, et al. Combined with Endocrine Therapy for the adjuvant treatment of HR+, HER2-, node-Positive, high-Risk, early breast cancer (MONARCH E). J Clin Oncol. 2020, 38(34):3987-3998.


  5. Johnston SRD, Toi M, O'Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (MONARCH E): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023, 24(1):77-90


  6. Goetz MP, Toi M, Huober J, et al. Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. Ann Oncol. 2024, 35(8):718-727.


  7. Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase III EMBER-3 trial. Ann Oncol. 2026, 37(4):532-543.


About the Author


Jaimee George holds a PhD in Microbiology and has published extensively in peer reviewed journals. As a scientific writer, she has developed systematic reviews, book chapters, review articles, and original research papers. Her professional interests include regulatory writing, medical communication tools, and case report development.


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