Evidence map›Paper›PMID 41339350›Full record

Trial reportNature communications2025

Letrozole, abemaciclib and metformin in endometrial cancer: a non-randomized phase 2 trial.

Panagiotis A Konstantinopoulos, Ningxuan Zhou, Richard T Penson, Tien V Le, Susana Campos, Carolyn Krasner, Alexi A Wright, Rebecca Porter, Neil Horowitz, Sara Bouberhan and 13 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03675893 (RESOLVE), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT03675893 phase2recruitingnot on this map

RESOLVE: A Multi-Cohort Phase 2 Study of Letrozole/Abemaciclib Alone and in Combination With Metformin and Gedatolisib

TypeinterventionalSponsorDana-Farber Cancer InstituteRan2018 to 2031Enrolled110ConditionsEndometrial CancerArmsLetrozole, Abemaciclib, LY3023414, Metformin, Gedatolisib
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. 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

23 authors.

Panagiotis A KonstantinopoulosDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Panagiotis_konstantinopoulos@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-1032-1479
Ningxuan ZhouDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Richard T PensonDepartment of Medical Oncology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Tien V LeDepartment of Oncology, Johns Hopkins University School of Medicine and Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, USA.
Susana CamposDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Carolyn KrasnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Alexi A WrightDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Rebecca PorterDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Neil HorowitzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Sara BouberhanDepartment of Medical Oncology, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0002-0315-2152
Joyce F LiuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Sarah HindenachDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Hannah SawyerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Lani KoppermannDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Martin HayesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Madeline PolakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0002-1331-3845
Meghan SheaDepartment of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0001-5262-1245
Page WidickDepartment of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Su-Chun ChengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Cesar CastroDepartment of Medical Oncology, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0002-1159-5658
Jan H BeumerDepartment of Oncology, Johns Hopkins University School of Medicine and Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, USA.
Ursula A MatulonisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Elizabeth K LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0001-7533-7853

Funding

Translational Research Central ServicesP30CA006973 · JOHNS HOPKINS UNIVERSITY · 1985 to 2025
$45.1M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). Primary objectives include objective response rate (ORR) and rate of progression-free survival (PFS) at 6 months (PFS6) while secondary objectives include PFS, overall survival, duration of response and toxicity. Twenty-five patients initiate protocol therapy [letrozole 2.5 mg orally (PO) once a day (qd), abemaciclib 150 mg PO twice a day (bid) and metformin 500 mg PO qd]. ORR is 32% (3 complete and 5 partial responses, 95% CI 14.9%-53.5%), Kaplan Meier estimate of PFS6 is 69.8% (95% CI 46.9%-84.3%) and median PFS is 19.4 months (95% CI 5.7 months-not estimable). No patients discontinue therapy because of toxicity. There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure.

Indexed as

AminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesEndometrial NeoplasmsLetrozoleMetforminAdultAgedAged, 80 and overFemaleHumansMiddle AgedProgression-Free SurvivalReceptors, EstrogenTreatment OutcomeabemaciclibAminopyridinesBenzimidazolesLetrozoleMetforminReceptors, Estrogen

Identifiers

PMID41339350
PMCPMC12795810

What Socratic holds

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Registered trials

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.