Abstract
Background
In monarchE, 2 years of abemaciclib plus endocrine therapy (ET) significantly reduced the risk of recurrence and mortality in patients with node-positive, high-risk hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. This analysis provides additional efficacy data based on nodal subgroups.
Patients and methods
Three nodal subgroups were analyzed in cohort 1, a population comprising 91% of the patients in monarchE: N1 high-risk (1-3 positive nodes with grade 3 tumors and/or tumor size ≥5 cm), N2 [4-9 positive axillary lymph node (ALN)], and N3 (≥10 positive ALN). Median follow-up was 76.8 months. Efficacy outcomes for invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) using Kaplan–Meier methods and baseline characteristics are reported for nodal subgroups.
Results
Kaplan–Meier analyses for IDFS and DRFS highlighted consistent and durable efficacy across nodal subgroups. Within the N1 high-risk group, 68.6% of tumors were grade 3; 57.6% of grade 3 tumors were <5 cm. In ET arm, recurrence risk in the N1 high-risk group was similar to N2.
Conclusions
The similar recurrence risk for patients in the N1 high-risk and N2 subgroups, and consistent efficacy across nodal subgroups, support addition of 2 years of adjuvant abemaciclib to ET to improve outcomes in patients meeting monarchE cohort 1 N1 high-risk, N2, or N3 criteria.
Key words: abemaciclib, early breast cancer, grade 3, nodal subgroups
Highlights
-
•
Abemaciclib+ET reduced the risk of recurrence and mortality in node-positive HR-positive, HER2-negative early breast cancer in monarchE.
-
•
Patients with N1 tumors that were grade 3 and/or ≥5 cm had similar recurrence and mortality risk to patients with N2 tumors.
-
•
Grade 3 disease, the highest mortality risk factor in real-world data in HR-positive, HER2-negative EBC, was present in 69% of N1 tumors.
-
•
Consistent efficacy across nodal subgroups (N1, N2, N3) supports adjuvant abemaciclib treatment in all eligible patients.
Introduction
Tumor spread to lymph nodes (LNs), most commonly presenting as axillary lymph node (ALN) positivity, is a major prognostic factor for recurrence and survival in early breast cancer (EBC).1 Although patients with more extensive nodal disease (N2, 4-9 LN; N3, ≥10 LN) are typically recommended to receive chemotherapy,2 management of patients with N1 (1-3 LNs) often requires additional risk assessment, such as genomic assays to identify those likely to benefit from chemotherapy.3
In the monarchE trial, 2 years of adjuvant abemaciclib plus endocrine therapy (ET) significantly reduced the recurrence and death risk in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative, node-positive EBC at high-risk of recurrence compared with ET alone. In the intent-to-treat population, with 76.2 months of median follow-up, abemaciclib is the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to demonstrate a statistically significant improvement in overall survival (OS) in the adjuvant setting [hazard ratio 0.842, 95% confidence interval (CI) 0.722-0.981, P = 0.027]. Abemaciclib + ET benefit in invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) was sustained well beyond the 2-year treatment duration of abemaciclib, with subgroup analyses showing consistent treatment benefit across nodal subgroups.4 Most regulatory approvals for adjuvant abemaciclib are based on monarchE cohort 1 (C1), which comprised 91% of enrolled patients5 and included patients with N2 or N3 disease without additional high-risk clinicopathological features and patients with N1 high-risk disease had a grade 3 tumor and/or tumor size ≥5 cm.
This report presents monarchE C1 LN subgroup data at the time of the primary OS data cut (cut-off date: 15 July 2025), including baseline characteristics and IDFS/DRFS outcomes by LN subgroup. These data provide a more in-depth understanding of recurrence risk and efficacy, which can inform clinical decisions.
Methods
Study design, patients, and assessments
Detailed study design, treatment, and procedures for the monarchE trial (NCT03155997) have been previously described.6,7 In monarchE cohort 1, patients were categorized into three nodal subgroups: N1 high-risk (1-3 positive nodes with grade 3 tumors and/or tumor size ≥5 cm), N2 (4-9 positive ALN), and N3 (≥10 positive ALN). Data reported here (cut-off date: 15 July 2025) are from primary OS analysis with a median follow-up of 76.8 months in cohort 1.
The primary endpoint of the trial was IDFS as defined by the Standardized Definitions for Efficacy End Points system. IDFS was calculated as the time from randomization until the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive disease, distant recurrence, contralateral invasive breast cancer, second primary nonbreast invasive cancer, or death from any cause. Key secondary endpoints included DRFS and OS. DRFS was calculated as the time from randomization until the first occurrence of metastatic disease or death from breast cancer. OS was defined as the time from randomization until the date of death from any cause.
Statistical analyses
Analyses of IDFS and DRFS were carried out to assess the relationship between efficacy outcomes and nodal subgroups using Kaplan–Meier methods, including estimated rates at 6 years. Hazard ratios and corresponding 95% CIs were estimated using a Cox proportional hazards model. The statistical analyses were carried out using SAS (version 9.2 or later; SAS Institute, Cary, NC).
Trial Oversight
The trial was designed by the sponsor, Eli Lilly and Company, in collaboration with a global steering committee. The protocol was approved by the ethical review board at each participating site. The trial was conducted in accordance with the principles of the Declaration of Helsinki, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines, and applicable laws and regulations. All participants provided written informed consent. The investigators gathered the data, while the sponsor monitored the conduct of the trial, received the data, and carried out all the analyses. The authors affirm the accuracy and completeness of the data and confirm that the trial was conducted in strict adherence to the approved protocol.
Results
Of 5120 patients in monarchE C1,5 1761 (34.4%) were N1 high-risk (1-3 ALN plus either grade 3 and/or tumor ≥5 cm), 2223 (43.4%) had N2 disease (4-9 ALN), and 1123 (21.9%) had N3. A total of 13 patients in C1 (7 in the abemaciclib + ET and 6 in the ET arm) were inadvertently enrolled with N0 disease. As these patients did not meet eligibility criteria for ALN subgroups, they were excluded from all ALN-based efficacy analyses. Patient disposition is provided in the supplement (Supplementary Figure S1, available at https://doi.org/10.1016/j.esmoop.2026.108549). Of note, in the ET arm, fewer patients completed treatment in the N3 subgroup, compared with N1 high-risk and N2 subgroups. This could be related to higher disease relapse in N3, which is to be expected, and therefore could explain the higher patient withdrawal in the ET arm.
Median age, menopausal status, and Eastern Cooperative Oncology Group were similar across all three nodal subgroups (Table 1). Among the North America/Europe-enrolled population, more patients presented with N1 high-risk disease (40.2%, 1064 of 2647) than in other regions (<30%). Among patients in the N1 high-risk subgroup, 42.2% received neoadjuvant chemotherapy, compared with 36.6% and 28.7% in the N2 and N3 groups, respectively. Conversely, adjuvant chemotherapy use was more common among patients with N2 and N3 disease (59.7% and 68.7%, respectively) compared with those in the N1 high-risk group (52.6%). Baseline characteristics are summarized in Table 1.
Table 1.
Baseline characteristics and prior therapies in nodal subgroups in the monarchE C1 population
| Characteristic | N1 high-risk (n = 1761) | N2 (n = 2223) | N3 (n = 1123) |
|---|---|---|---|
| Age, years (median, range) | 51 (23-86) | 51 (22-89) | 53 (23-88) |
| Menopausal status at diagnosis, n (%) | |||
| Peri/premenopausal | 793 (45.0) | 983 (44.2) | 437 (38.9) |
| Postmenopausal | 968 (55.0) | 1240 (55.8) | 686 (61.1) |
| Baseline ECOG, n (%) | |||
| 0 | 1507 (85.6) | 1875 (84.3) | 940 (83.7) |
| 1 | 252 (14.3) | 344 (15.5) | 183 (16.3) |
| Geographic distribution, n (%) | |||
| North America/Europe | 1064 (60.4) | 1059 (47.6) | 524 (46.7) |
| Asia | 290 (16.5) | 483 (21.7) | 271 (24.1) |
| Other | 407 (23.1) | 681 (30.6) | 328 (29.2) |
| Prior chemotherapy, n (%) | |||
| Neoadjuvant | 743 (42.2) | 814 (36.6) | 322 (28.7) |
| Adjuvant | 927 (52.6) | 1328 (59.7) | 772 (68.7) |
| No chemotherapy | 91 (5.2) | 81 (3.6) | 29 (2.6) |
| Prior radiotherapy, n (%) | |||
| Yes | 1628 (92.4) | 2175 (97.8) | 1106 (98.5) |
| No | 133 (7.6) | 48 (2.2) | 17 (1.5) |
| Ki-67, n (%) | |||
| <20% | 502 (28.5) | 947 (42.6) | 460 (41.0) |
| ≥20% | 859 (48.8) | 741 (33.3) | 400 (35.6) |
| Missing | 400 (22.7) | 535 (24.1) | 263 (23.4) |
| Histology, n (%) | |||
| Lobular | 186 (10.6) | 277 (12.5) | 226 (20.1) |
| Ductal | 1270 (72.1) | 1510 (67.9) | 692 (61.6) |
| Other | 305 (17.3) | 436 (19.6) | 205 (18.3) |
Percentages do not include missing data and may not add up to 100%.
ECOG, Eastern Cooperative Oncology Group.
Distribution of tumor grade and other pathological features varied across nodal subgroups. Within the N1 high-risk subgroup, 68.6% of patients had grade 3 tumors, consisting of 57.6% of tumors <5 cm group and 10.9% of tumors in ≥5 cm group. In contrast, grade 3 tumors were less frequent in patients in the N2 (26.5%) or N3 (27.5%) subgroups (Figure 1). Ki-67 values ≥20% were also more common in the N1-high-risk group than in N2 or N3 subgroups (Table 1). The distribution of ductal versus lobular histology was similar between the N1 high-risk and N2 groups, whereas the N3 subgroup included a higher proportion of lobular tumors (Table 1).
Figure 1.
Distribution of tumor grade and tumor size by ALN in monarchE C1. ∗Ineligible patients or eligible for cohort 2 and inadvertently assigned to C1. Values that do not add up to 100% are due to rounding or missing data. ALN, axillary lymph node.
To better understand the long-term recurrence risk on standard ET and treatment benefit of abemaciclib plus ET, Kaplan–Meier analyses were carried out for IDFS and DRFS for each nodal subgroup at 76.8 months of median follow-up. At this data cut, the recurrence risk was robustly assessed up to 6 years, given >500 patients were followed up for up to 6 years. In the ET alone arm, similar recurrence risk was observed between the N1 high-risk and N2 groups (6-year IDFS event rates: 21.6% and 25.4%), whereas patients with N3 disease had a poorer prognosis (6-year IDFS event rate: 38.1%). A similar pattern of 6-year DRFS event rates was observed: N1 high-risk (17.7%), N2 (22.3%), and N3 (34.9%). Abemaciclib treatment benefit was consistent across all nodal groups (interaction P values: 0.82 for IDFS, 0.85 for DRFS), with sustained curve separation for both IDFS and DRFS (Figure 2).
Figure 2.
Kaplan–Meier plots of IDFS and DRFS by nodalsubgroupin C1. (A) Kaplan–Meier curve of IDFS in N1 high-risk. (B) Kaplan–Meier curve of IDFS in N2. (C) Kaplan–Meier curve of IDFS in N3. (D) Kaplan–Meier curve of DRFS in N1 high-risk. (E) Kaplan–Meier curve of DRFS in N2. (F) Kaplan–Meier curve of DRFS in N3. Hazard ratios, event numbers, and 6-year rates from Johnston et al.4 are included for context. DRFS, distant recurrence-free survival; ET, endocrine therapy; IDFS, invasive disease-free survival.
Discussion
With a median follow-up of 76.8 months in the monarchE C1 population, the addition of 2 years of adjuvant abemaciclib to ET provided a sustained, clinically meaningful reduction in the risk of recurrence in patients with LN-positive HR-positive, HER2-negative EBC, irrespective of the degree of LN involvement. Kaplan–Meier analyses by nodal status presented here highlight the consistent treatment benefit across ALN subgroups for IDFS and DRFS, reinforcing the robustness of the benefit of abemaciclib over long-term follow-up. A consistent OS benefit across nodal subgroups [hazard ratio of 0.88 (0.65, 1.18), 0.85 (0.66, 1.09), and 0.73 (0.56, 0.96) in N1 high-risk, N2, and N3, respectively] has previously been reported.4
Baseline characteristics by nodal status suggest different risk by geography. Patients in Asia were more likely to be premenopausal and present with N2/N3 disease (72.2%), which is associated with more aggressive disease.8 Although patients with N1 disease by anatomical staging are generally considered to have a lower recurrence risk than those with N2 or N3 disease,1 recurrence risk varies within N1 disease when additional pathological features are considered.9 In monarchE C1, patients with N1 disease were considered high-risk if ≥1 additional high-risk feature (grade 3 and/or tumor ≥5 cm) was identified. Real-world US Surveillance, Epidemiology, and End Results data showed that grade 3 is the most important risk factor for mortality in HR-positive, HER2-negative EBC.10 In a US Flatiron Health real-world data analysis, patients with N1 high-risk features as defined in the monarchE inclusion criteria had approximately double the recurrence and mortality risk at 5 years on standard of care ET than patients with N1 without these high-risk features. In this real-world dataset, grade 3 was present in 80.9% of tumors in the N1 high-risk group.9 In monarchE C1, 68.6% of patients in the N1 high-risk group had grade 3 disease and their recurrence risk was similar to N2 when receiving ET only, underscoring the high unmet need in both nodal groups. Notably, patients with N3 disease had poorer prognosis than those in N1 high-risk or N2 subgroups. Consistent with these results, 6-year mortality risk with ET only in monarchE was similar between N1 high-risk and N2 subgroups (10.6% and 11.2%), and higher in the N3 subgroup (20.0%).4 In total, these data suggest that in addition to patients with N2/N3 disease, patients with N1 disease that exhibit other high-risk criteria (grade 3 and/or large tumor size) should also be considered for adjuvant abemaciclib given the consistent IDFS, DRFS, and OS treatment benefit across nodal subgroups.
In a US Flatiron Health study conducted during the period when abemaciclib was the only approved adjuvant CDK4/6i, 60.0% of patients meeting monarchE C1 criteria and eligible for adjuvant abemaciclib were not receiving this treatment,9 suggesting that some patients are not receiving optimal therapy. Underutilization of abemaciclib reaches 69.1% in patients with N1 high-risk disease.
Adverse event profiles are also considered when deciding whether to add adjuvant CDK4/6i. Abemaciclib side effects are reversible and generally manageable using early dose reductions without impacting efficacy.11,12 A dose escalation strategy has been developed to help establish patients on treatment and improve adherence.13
The baseline characteristics, recurrence-risk data, and efficacy details shared here are important for clinicians and provide data on the efficacy of CDK4/6i in the adjuvant setting for node-positive disease, even in those patients with N1 involvement but with high-risk features. The similar recurrence and mortality risks for patients in the N1 high-risk and N2 subgroups, together with the consistent IDFS, DRFS, and OS benefits across nodal subgroups,4 indicate that treatment optimization across all nodal categories with adjuvant abemaciclib is needed to reduce these risks and improve outcomes.
Acknowledgements
This work was supported by Eli Lilly and Company. Eli Lilly had a role in the design of the study and collection, analysis, and interpretation of data and in writing. The authors thank patients and their families as well as the investigators and their support staff for participating in this trial. Finally, the authors are grateful for the time and efforts of the monarchE Executive and Steering Committees. All writing, editorial assistance, and statistical analysis were funded by Eli Lilly and Company. Medical writing and editorial support were provided by Joana Cruz Pereira, PhD, an employee of Eli Lilly.
Data availability
Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank, or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org. Preliminary data related to this work was presented at SABCS 2025.
Funding
This work was supported by Eli Lilly and Company (no grant number).
Declaration of AI and AI-assisted technologies in the writing process
During the preparation of this work, the authors used CoPilot for editing purposes. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.
Disclosure
JC reports a relationship with Eli Lilly and Company that includes consulting or advisory and speaking and lecture fees; AstraZeneca that includes board membership, funding grants, speaking and lecture fees, and travel reimbursement; AbbVie, Bioasis, Biocon, BioNTech, Bliss Biopharmaceutical, Boehringer Ingelheim, Bridgebio, Circle Pharma, Clovis Oncology, Delcath Systems, Ellipses, ExpreS2ion Biotechnologies, Gemoab, Hexagon Bio, Hibercell, Menarini, Jazz Pharmaceuticals, Relay Therapeutics, Reveal Genomics, Scorpion Therapeutics, Seattle Genetics, and Zymeworks that include consulting or advisory; Gilead that includes consulting or advisory, speaking and lecture fees, and travel reimbursement; LEUKO that includes consulting or advisory and equity or stocks; Merck Sharp & Dohme (MSD) and Roche that include consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement; MAJ3 Capital that includes equity or stocks; Ariad Pharmaceuticals, Baxalta, Bayer Healthcare, Eisai, Guardant Health, IQVIA, GmbH, Servier, Pigur Therapeutics, and Queen Mary University of London that include funding grants; Pfizer and Eisai Inc that include funding grants, speaking and lecture fees, and travel reimbursement; Daiichi Sankyo Inc, Novartis, and Stemline Therapeutics Inc that include speaking and lecture fees and travel reimbursement; and Zuellig Pharma that includes speaking and lecture fees. SJ reports a relationship with Pfizer, Eli Lilly and Company, AstraZeneca, Roche, and Novartis that include consulting or advisory and funding grants; Genentech that includes funding grants. MM reports a relationship with Pfizer, Novartis, MSD, Eli Lilly and Company, Bayer, Roche, GlaxoSmithKline (GSK), and Menarini that include consulting or advisory. SMT reports a relationship with Novartis, Daiichi Sankyo, Jazz Pharmaceuticals, Genentech Roche, Pfizer Seagen, and Menarini Stemline that include consulting or advisory and funding grants; Eli Lilly and Company, AstraZeneca, and Gilead that include consulting or advisory, funding grants, and travel reimbursement; Merck, Eisai, Blueprint Medicines, Reveal Genomics, Sumitovant BioPharma Inc, Artios Pharma, Aadi Bio, Bayer, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas Inc, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson & Johnson Ambrx, Bicycle Therapeutics, BeOne Therapeutics, Mersana, Summit Therapeutics, Avenzo therapeutics, Aktis Oncology, Boehringer Ingelheim, Celcuity, Inc., Samsung Bioepis Co., Ltd., Olema Pharmaceuticals, Inc., Tempus, Boundless Bio Inc, Denali Therapeutics Inc, and Bristol Myers Squibb (BMS)/SystImmune that include consulting or advisory; Jazz Pharmaceuticals, Roche, Pfizer, and Arvinas Inc that include travel reimbursement; BMS Co, Exelsis, NanoString Technologies, and OncoPep that include funding grants. MPG reports a relationship with AXIS, BroadcastMed, Dava Oncology, IDEOlogy Health, MJH Life Sciences, PeerView, Physicians’ Education Resource, Research to Practice, Total Health Conferencing, Amneal Pharmaceuticals, AstraZeneca Pharmaceuticals LP, AstraZeneca UK Limited, Ataraxis AI, BeiGene USA, Biotheranostics, eChinaHealth, EcoR1, Engage Health Media, Genentech, Incyclix Bio, Laekna, Novartis, RNA Diagnostics, Seattle Genetics, Stemline Therapeutics, TerSera Therapeutics Ampility Health, and Lilly that include consulting or advisory; AstraZeneca, BioTheryX, Pfizer, Puma, and Sermonix Pharmaceuticals that include consulting or advisory and funding grants; Eli Lilly and Company that include consulting or advisory, funding grants, and travel reimbursement; Atossa Therapeutics, Loxo, SimBioSys, and 858 Therapeutics Inc that include funding grants; and consulting fees to Mayo Clinic from 858 Therapeutics, Inc. HSR reports a relationship with Mylan Viatris, Chugai Pharma, Napo Pharmaceuticals, Sanofi, BMS, and Helsinn Therapeutics that include consulting or advisory; OBI Pharma, Pfizer, Novartis, Eli Lilly and Company, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Roche Genentech, and Stemline Therapeutics that include funding grants. JS reports a relationship with Daiichi Sankyo that includes equity or stocks; Seagen, MSD, Roche, Pfizer, Novartis, AstraZeneca, Lilly, GSK, Boehringer Ingelheim, Daiichi Sankyo, Qurient, Dragonfly, Eikon, Gilead, Celcuity, BMS, HLB Life Science, Sermonix, Olema, Hanmi, ILDONG, and Samyang that include funding grants. MZ reports a relationship with AstraZeneca, AbbVie, Novartis, Pfizer, and Roche that include consulting or advisory and speaking and lecture fees; Esai that includes consulting or advisory; BMS, Gilead, Janssen, and Stemline that include consulting or advisory; Eli Lilly and Company and Takeda that include speaking and lecture fees. KMV reports a relationship with Amgen, Novartis, Daiichi Sankyo, Ipsen, and Astellas that include consulting or advisory; MSD, GSK, Pfizer, BMS, Roche, AstraZeneca, and Eli Lilly and Company that include consulting or advisory and funding grants; BeOne Therapeutics, Janssen, Seagen, Servier, Mabxience, Incyte, Gilead, and Stemline Therapeutics that include funding grants. AC reports a relationship with Novotech that includes consulting or advisory. HK reports a relationship with Medpraxis Ltd that includes board membership; Pfizer, Roche, MSD that include consulting or advisory, funding grants, and travel reimbursement; Enorasis that includes consulting or advisory and travel reimbursement; Amgen and Sanofi that include consulting or advisory and funding grants; GSK, Novartis, Summit Therapeutics, and Farmaserb-Lilly that include funding grants. BRG and SA report relationships with Eli Lilly and Company that includes employment and equity or stocks. PN reports grants paid to institution from Kom op Tegen Kanker and Think Pink; reports consultation fees paid to the institution from Pfizer, Novartis, Eli Lilly, Roche, AstraZeneca, and Gilead; reports participation in advisory boards paid to the institution: Pfizer, Novartis, Eli Lilly, Roche, and Bayer. All remaining authors have declared no conflicts of interest.
Supplementary data
References
- 1.Pan H., Gray R., Braybrooke J., et al. 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–1846. doi: 10.1056/NEJMoa1701830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Gradishar W.J., Moran M.S., Abraham J., et al. Breast cancer, version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(5):331–357. doi: 10.6004/jnccn.2024.0035. [DOI] [PubMed] [Google Scholar]
- 3.Kalinsky K., Barlow W.E., Gralow J.R., et al. 21-Gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med. 2021;385(25):2336–2347. doi: 10.1056/NEJMoa2108873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Johnston S., Martin M., O’Shaughnessy J., et al. Overall survival with abemaciclib in early breast cancer. Ann Oncol. 2026;37(2):155–165. doi: 10.1016/j.annonc.2025.10.005. [DOI] [PubMed] [Google Scholar]
- 5.Rastogi P., O’Shaughnessy J., Martin M., et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol. 2024;42(9):987–993. doi: 10.1200/JCO.23.01994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Johnston S.R.D., 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Johnston S.R.D., Toi M., O’Shaughnessy J., et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77–90. doi: 10.1016/S1470-2045(22)00694-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Toi M., Kim S.-B., Chiu J.W.Y., et al. 201P abemaciclib (abema) combined with adjuvant endocrine therapy (ET) in patients from monarchE in Asia with high-risk early breast cancer (EBC) ESMO Open. 2025;10 [Google Scholar]
- 9.Tolaney S.M., Sammons S., Sandoval-Leon A., et al. Exploring the treatment gap and outcome risks in patients with node-positive, high-risk, HR-positive, HER2-negative early breast cancer: analyses of real-world data. ESMO Open. 2026;11(2) doi: 10.1016/j.esmoop.2025.106021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Nelson D.R., Brown J., Morikawa A., Method M. Breast cancer-specific mortality in early breast cancer as defined by high-risk clinical and pathologic characteristics. PLoS One. 2022;17(2) doi: 10.1371/journal.pone.0264637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Rugo H.S., O’Shaughnessy J., Boyle F., et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022;33(6):616–627. doi: 10.1016/j.annonc.2022.03.006. [DOI] [PubMed] [Google Scholar]
- 12.Goetz M.P., Cicin I., Testa L., et al. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer. 2024;10(1):34. doi: 10.1038/s41523-024-00639-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Mayer E.L., Trapani D., Kim S.-E., et al. TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer. Ann Oncol. 2026;37(1):117–124. doi: 10.1016/j.annonc.2025.09.141. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank, or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org. Preliminary data related to this work was presented at SABCS 2025.