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Verzenios ® (abemaciclib)
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Is Verzenios® (abemaciclib) efficacy impacted by dose reduction due to adverse events?
PFS was similar for patients who had to reduce the abemaciclib dose due to adverse events in MONARCH 2 and MONARCH 3. In monarchE, patients stratified by relative dose intensity had consistent 4-year IDFS rates.
Efficacy following dose reduction in Early breast cancer - monarchE
We analyzed data from 2791 patients treated with abemaciclib in early breast cancer to explore how reducing the dose affects its effectiveness. We used a time-dependent Cox proportional hazard model to study how dose changes over time affect invasive disease-free survival (IDFS). The data was collected until July 1, 2022.1
In monarchE, 43.6% of patients required dose reductions to proactively manage adverse events. Up to 2 dose reductions (100 or 50 mg) were permitted before discontinuation.1
Patients were divided into three equal-sized groups based on the average daily dose they received relative to the full dose of 150 mg twice daily (relative dose intensity, RDI). IDFS rates were estimated using Kaplan-Meier method within each subgroup.1
Of the 2791 patients treated with abemaciclib
- 832 (30%) had one dose reduction, and
- 389 (14%) had two dose reductions.1
Older patients (≥65 years old) and those with more co-existing health issues (≥4 co-morbidities) were more likely to require dose reductions (56% and 50% respectively).1
Patients with dose reductions were more likely to continue abemaciclib treatment compared to those without reductions.1 The percentage of patients still on treatment ˃6 months by number of dose reductions was
- 81% (0 reductions, N=1570)
- 90% (1 reduction, N=832), and
- 86% (2 reductions, N=389).1
Efficacy results following dose reductions
The invasive disease-free survival (IDFS) rates were similar across all dose reduction groups. The 4-year IDFS rates were consistent, 87.1% vs 86.4% vs 83.7% from the lowest RDI group to the highest) across the 3 RDI groups (0-66% vs 66%-93% vs ≥93%)().1
The efficacy of abemaciclib was not compromised by dose reductions. The full 150 mg dose was comparable to reducing the dose to 100 mg or 50 mg (HR = 0.905; 95% CI = 0.727, 1.125) ().1
Efficacy Endpoint |
HR (95% CI) Staying at full dose versus Being reduced to lower doses |
ITT |
|
IDFS |
0.905 (0.727, 1.125) |
DRFS |
0.942 (0.742, 1.195) |
Cohort 1 |
|
IDFS |
0.899 (0.718, 1.125) |
DRFS |
0.958 (0.750, 1.223) |
Abbreviations: DRFS = distant relapse-free survival; HR = hazard ratio; IDFS = invasive disease-free survival; ITT = intent-to-treat.
Efficacy following dose reduction in metastatic or advanced breast cancer - MONARCH 2 and MONARCH 3
We performed a time-dependent covariate analysis to examine the association between the current dose level (150 mg, 100 mg, and 50 mg) and PFS in the MONARCH 2 and MONARCH 3 trials.
Compared to being treated at the 150 mg dose level, patients in MONARCH 2 experienced no difference in PFS when their dose was reduced to
- 100 mg (HR=1.033; 95% CI: 0.679-1.572; p=.8793), or
- 50 mg (HR=0.923; 95% CI: 0.499-1.706; p=.7973).3
Likewise, patients in MONARCH 3 experienced no difference in PFS when their dose was reduced to
- 100 mg (HR=0.764; 95% CI: 0.467-1.251), or
- 50 mg (HR=0.985; 95% CI: 0.511-1.902).3
Efficacy of Lower Starting Doses at Treatment Initiation
We have no information available on starting doses of less than 150 mg.
The recommended dose of abemaciclib is 150 mg twice daily in combination with endocrine therapy.4
References
1O’Shaughnessy J, Cicin I, Testa L, et al. Impact of dose reductions on efficacy of adjuvant abemaciclib for patients with high-risk early breast cancer (EBC): analyses from the monarchE study. Poster presented at: European Society of Medical Oncology (ESMO); October 20-24, 2023; Madrid, ES. Accessed October 19, 2023. https://cslide.ctimeetingtech.com/esmo2023/attendee/confcal_2/presentation/list?q=274P
2Hamilton E, Kim J, Eigeliene N, et al. Efficacy and safety results by age in monarchE: adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Poster presented at: 59th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 2-6, 2023; Chicago, IL. Accessed May 22, 2023. https://meetings.asco.org/abstracts-presentations/218406
3Rugo HS, Sledge GW Jr, Johnston S, et al. The association of early toxicity and outcomes for patients treated with abemaciclib. J Clinical Oncol. 2018;36(15 suppl):1053. https://doi.org/10.1200/JCO.2018.36.15_suppl.1053
4Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
Date of Last Review: 31 August 2023