Evidence map›Paper›PMID 41785668›Full record

Trial reportESMO open2026

Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in ER-positive, HER2-negative advanced breast cancer: an indirect treatment comparison of three phase III trials.

K Jhaveri, F C Bidard, K Kalinsky, P Neven, H S Rugo, S M Tolaney, L M Litchfield, C C von Laue, S Traore, F Sapunar and 2 more

Abstract readClinical Trial, Phase IIIComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

K JhaveriMemorial Sloan Kettering Cancer Center, New York, USA. Electronic address: jhaverik@mskcc.org.
F C BidardInstitut Curie, Paris and Saint Cloud, France.
K KalinskyWinship Cancer Institute of Emory University, Atlanta, USA.
P NevenDepartment of Oncology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
H S RugoCity of Hope, Duarte, USA.
S M TolaneyDana Farber Cancer Institute, Boston, USA.
L M LitchfieldEli Lilly and Company, Indianapolis, USA.
C C von LaueEli Lilly and Company, Indianapolis, USA.
S TraoreEli Lilly and Company, Indianapolis, USA.
F SapunarEli Lilly and Company, Indianapolis, USA.
Y LiEli Lilly and Company, Indianapolis, USA.
J O'ShaughnessyBaylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute, Dallas, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundThe EMBER-3 trial demonstrated significant progression-free survival (PFS) benefit for imlunestrant + abemaciclib versus imlunestrant alone in patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) with disease recurrence/progression during prior aromatase inhibitor ± cyclin-dependent kinase 4/6 inhibitor (AI ± CDK4/6i) treatment. The phase III MONARCH 2 and postMONARCH trials demonstrated the superiority of fulvestrant + abemaciclib versus fulvestrant in CDK4/6i-naïve and pretreated patients, respectively. The efficacy of imlunestrant + abemaciclib versus fulvestrant + abemaciclib has not been directly evaluated in randomized controlled trials. In the absence of head-to-head trial data, indirect treatment comparison (ITC) analyses allow fair evaluation of between-trial efficacy. This study aimed to determine the relative efficacy of imlunestrant + abemaciclib versus fulvestrant + abemaciclib through ITC of the EMBER-3, MONARCH 2, and postMONARCH trials. MATERIALS AND

methodsTo compare investigator-assessed PFS between imlunestrant + abemaciclib and fulvestrant + abemaciclib, three ITC methods-Bucher, matching-adjusted indirect comparison (MAIC), and propensity score matching (PSM)-were employed using individually matched patient-level data from the EMBER-3, MONARCH 2, and postMONARCH trials. Ten prognostic and predictive factors were selected as baseline covariates. The standard Bucher method had no population adjustment, whereas PSM and MAIC were population-adjusted. The MAIC analysis adjusted the pooled MONARCH 2/postMONARCH population to match the EMBER-3 population. The PSM matched the propensity score between the EMBER-3 and pooled MONARCH 2/postMONARCH populations.

resultsBaseline characteristics were well balanced across adjusted populations by MAIC and PSM. Though not powered for formal hypothesis testing, PFS favored imlunestrant + abemaciclib versus fulvestrant + abemaciclib across all three ITC methods. Hazard ratios (95% confidence intervals) for Bucher, MAIC, and PSM were 0.77 (0.58-1.04), 0.77 (0.55-1.06), and 0.83 (0.56-1.22), respectively.

conclusionIn this ITC analysis of patient-level data from three phase III trials, although not powered for formal hypothesis testing, the all-oral targeted combination therapy imlunestrant + abemaciclib showed a consistent numerical reduction in the risk of disease progression or death compared with fulvestrant + abemaciclib in patients with ER-positive/HER2-negative ABC previously treated with endocrine therapy ± CDK4/6i.

Indexed as

AminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesBreast NeoplasmsFulvestrantErb-b2 Receptor Tyrosine KinasesFemaleHumansReceptors, EstrogenabemaciclibAminopyridinesBenzimidazolesErb-b2 Receptor Tyrosine KinasesFulvestrantReceptors, EstrogenabemaciclibEMBER-3fulvestrantimlunestrantindirect treatment comparisonprogression-free survival

Identifiers

PMID41785668
PMCPMC12972957

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.