Evidence map›Paper›PMID 41793559›Full record

ArticleBreast cancer research and treatment2026

Comparative effectiveness of CDK4/6 inhibitors in metastatic breast cancer: using the target trial emulation framework to investigate overall survival in routine care.

Adam M Brufsky, Richard S Finn, Otto Metzger, Rodrigo Goncalves, Cynthia Huang-Bartlett, Sameet Sreenivasan, Ula Nur, Jessica Davies, Alex Grigorenko, Gráinne H Long

Abstract readComparative Study
In one paragraph

Article in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

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

10 authors.

Adam M BrufskyDivision of Hematology/Oncology, University of Pittsburgh School of Medicine & University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-8080-7960
Richard S FinnDivision of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2494-2126
Otto MetzgerBreast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0792-0320
Rodrigo GoncalvesLate Development, Oncology R&D, AstraZeneca, Barcelona, Spain.ORCID http://orcid.org/0000-0002-3513-0214
Cynthia Huang-BartlettLate Development, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0003-2003-2213
Sameet SreenivasanClinical Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA. sameet.sreenivasan@astrazeneca.com.ORCID http://orcid.org/0000-0001-5785-8815
Ula NurClinical Data Sciences, Oncology R&D, AstraZeneca, Cambridge, UK.ORCID http://orcid.org/0000-0001-8203-7226
Jessica DaviesClinical Data Sciences, Oncology R&D, AstraZeneca, Barcelona, Spain.
Alex GrigorenkoClinical Data Sciences, Oncology R&D, AstraZeneca, New York, NY, USA.ORCID http://orcid.org/0009-0000-6723-8695
Gráinne H LongClinical Data Sciences, Oncology R&D, AstraZeneca, Cambridge, UK.ORCID http://orcid.org/0009-0001-4074-4536

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) is the recommended first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). CDK4/6i head-to-head trials have not been conducted, and randomized controlled trials (RCTs) report inconsistent overall survival (OS) results despite similar effects on the primary endpoint of progression-free survival. Real-world evidence can complement RCTs but selection biases and confounders can challenge interpretation. Target trial emulation applies the principles of RCTs to observational data to overcome such challenges. We emulated a hypothetical target trial to investigate whether causal differences in OS between patients receiving first-line CDK4/6i plus AI exist in the real-world clinical setting.

methodsWe used de-identified data (Flatiron Health mBC Enhanced Data Mart) from patients ≥ 18 years old at primary diagnosis who were treated with first-line palbociclib/ribociclib/abemaciclib plus AI for mBC between 2018 and 2024. Statistical adjustments included stabilized inverse-probability weighting (sIPTW), investigation of missing data mechanisms, and analyses for unmeasured confounders.

results2626 patients were included (palbociclib n = 1686; ribociclib n = 537; abemaciclib n = 403). After sIPTW, baseline characteristics were balanced between groups and there was no observable difference in real-world OS (ribociclib vs palbociclib, adjusted hazard ratio 1.00, 95% CI: 0.81-1.24; abemaciclib v palbociclib: 0.91, 95% CI: 0.74-1.14). Results were consistent after sensitivity analyses.

conclusionUsing target trial emulation, real-world OS is similar with palbociclib/ribociclib/abemaciclib plus AI. These findings may contribute to the development of combination strategies to improve clinical outcomes and to guide clinical decision-making.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Protein Kinase InhibitorsAdultAgedAminopyridinesAromatase InhibitorsBenzimidazolesFemaleHumansMiddle AgedNeoplasm MetastasisPiperazinesPurinesabemaciclibAminopyridinesAromatase InhibitorsBenzimidazolesCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6palbociclibPiperazinesProtein Kinase InhibitorsPurinesPyridinesribociclibCyclin-dependent kinase 4/6Metastatic breast cancerOverall survivalReal-world dataTarget trial emulation

Identifiers

PMID41793559
PMCPMC12967648

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.