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Verzenios ® (abemaciclib)
This information is intended for UK registered healthcare professionals only in response to your search for information. For current information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk
How to manage pneumonitis in Verzenios® (abemaciclib) treated patients?
Based on the grade of interstitial lung disease (ILD)/pneumonitis, abemaciclib dose modifications may be required as outlined below.
Pneumonitis and Abemaciclib
Pneumonitis/ILD
Pneumonitis is a general term that refers to inflammation of the lungs. The term interstitial lung disease (ILD) is an imprecise clinical term that refers to a group of more than 200 chronic lung disorders characterized by inflammation of the lung tissue, which often leads to scarring.1,2
In clinical practice, the terms ILD and pneumonitis are often used interchangeably.
Interstitial lung disease can be caused by autoimmune diseases, genetic abnormalities (eg, Hermansky–Pudlak syndrome) and long-term exposures to hazardous materials (eg, medications such as bleomycin, occupational exposures such as asbestos, tobacco smoke, or agents in the environment that cause an immune reaction called hypersensitivity pneumonitis).
However, the cause of ILD is mostly unknown and the lung manifestations are described as idiopathic interstitial pneumonia.1
Drug-induced interstitial lung disease (DIILD) occurs when exposure to a drug causes inflammation and eventually fibrosis of the lung interstitium.
DIILD has been associated with chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents.
Cancer drugs account for approximately 23% to 51% of DIILD cases.3 It becomes challenging to identify potentially causative agents in oncology when drugs are combined with other agents, or given in association with radiotherapy; the risk of developing DIILD may be increased when causative agents are combined.3
Mechanism of Action and Etiology of ILD
The reasons patients develop ILD/pneumonitis when they are taking anticancer medications are not fully understood. There can also be multiple confounding factors, especially in cancer treatment, where multiple drugs are often administered at the same time.
Based on the mechanism of action of abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor and the etiology of ILD, there is no known mechanistic explanation for an association of abemaciclib and ILD.4
An exploratory study was conducted to identify whether specific human leukocyte antigen (HLA)alleles were associated with abemaciclib-induced ILD. Alleles assessed included HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, and -DPB1. There were 28 alleles that had a frequency of ≥10% in cases of ILD, but it was determined that there was no significant association between carriage of those HLA alleles and development of ILD.5
Management Recommendations for ILD/Pneumonitis
The management of ILD/pneumonitis may require dose interruptions or dose reductions or both. Below you will find information about the recommendations on dose adjustments.
Please review the Verzenios Summary of Product Characteristics, particularly the sections:
• 4.2 Posology and method of administration
• 4.4 Special warnings and precautions for use
Incidence of Pneumonitis in the MONARCH Trials and Postmarketing Reports
Across the MONARCH clinical trials, the incidence of ILD/pneumonitis was
In the abemaciclib + fulvestrant arm (n=441) of MONARCH 2
- 3 (0.7%) events were Grade ≥3
- 4 (0.9%) events were reported as a serious adverse event (SAE)
- there were no reported dose reductions, and
- 2 (0.4%) discontinuations were reported due to ILD/pneumonitis events.6
In the abemaciclib + nonsteroidal aromatase inhibitor (NSAI) arm (n=327) of MONARCH 3
- 4 (1.2%) events were Grade ≥3
- 6 (1.8%) events were reported as an SAE
- 2 (0.6%) patients required dose reductions due to an ILD/pneumonitis event, and
- 4 (1.2%) patients discontinued due to an ILD/pneumonitis event.6
In the MONARCH 2 trial, out of 9 patients who received abemaciclib plus fulvestrant and experienced an ILD/pneumonitis event, 8 patient had lung metastases and 6 patients had prior radiotherapy. In the MONARCH 3 trial, out of 17 patients who received abemaciclib plus NSAI and experienced an ILD/pneumonitis event, 6 patients had lung metastases and 9 patients had prior radiotherapy.6
Deaths in the MONARCH Clinical Trials
Death due to ILD/pneumonitis in abemaciclib-treated patients was reported
- in 1 patient in MONARCH 1
- in 2 patients (0.5%) in MONARCH 2, and
- in 1 patient (0.3%) in MONARCH 3.7
Incidence of Pneumonitis in Postmarketing Reports
Interstitial lung disease/pneumonitis was identified as a common (≥1.0% to <10%) adverse drug reaction based on spontaneous data from postmarketing reports.4
A meta-analysis, which included 12 randomized controlled studies, including 7 studies with abemaciclib, found the incidence of all-grade ILD/pneumonitis in patients treated with abemaciclib to be 2.5%.8
References
1Anthimopoulos M, Christodoulidis S, Ebner L, et al. Lung pattern classification for interstitial lung diseases using a deep convolutional neural network. IEEE Trans Med Imaging. 2016;35(5):1207-1216. http://dx.doi.org/10.1109/tmi.2016.2535865
2Bourke SJ. Interstitial lung disease: progress and problems. Postgrad Med J. 2006;82(970):494-499. http://dx.doi.org/10.1136/pgmj.2006.046417
3Skeoch S, Weatherley N, Swift AJ, et al. Drug-induced interstitial lung disease: a systematic review. J Clin Med. 2018;7(10). http://dx.doi.org/10.3390/jcm7100356
4Data on file, Eli Lilly and Company and/or one of its subsidiaries.
5Imamura C, Mushiroda T, Hosonaga M, et al. An exploratory study on prediction of risk for abemaciclib-induced interstitial lung disease or hepatotoxicity by specific human leukocyte antigen alleles [abstract]. J Clin Onc. 2024:42(16)(suppl):3087. https://doi.org/10.1200/JCO.2024.42.16_suppl.3087
6Rugo HS, Huober J, Garcia-Saenz JA, et al. Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. Oncologist. 2021;26(1):e53-e65. http://dx.doi.org/10.1002/onco.13531
7Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.
8Zhang Y, Ma Z, Sun X, et al. Interstitial lung disease in patients treated with cyclin-dependent kinase 4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials. The Breast. 2022;62:162-169. https://doi.org/10.1016/j.breast.2022.02.011
Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.
Date of Last Review: 02 October 2024