Evidence map›Paper›PMID 40804745›Full record

SynthesisBreast cancer research : BCR2025

Comparative efficacy of first- versus second-line CDK4/6 inhibition in hormone receptor-positive, HER2-negative metastatic breast cancer.

Lis Victoria Ravani, Zahra Bagheri, Adam M Brufsky, Isabella Michelon, Ruth O'Regan, Maryam Lustberg, Hyo Han, Ming Wang, Seth A Wander

Erratum issuedAbstract readMeta-AnalysisSystematic ReviewComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Lis Victoria Ravani *Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
Zahra Bagheri *Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Adam M BrufskyDivision of Hematology/Oncology, Comprehensive Breast Cancer Center, University of Pittsburgh Medical Center, Magee Women's Center, Pittsburgh, PA, USA.
Isabella MichelonDivision of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, Pelotas, USA.
Ruth O'ReganUniversity of Rochester Medical Center, Rochester, NY, USA.
Maryam LustbergMedical Oncology, Yale Cancer Center, Yale University, New Haven, CT, USA.
Hyo HanDepartment of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Ming WangDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Seth A WanderDivision of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School Massachusetts General Hospital, 55 Fruit St. Yawkey 9A, Boston, 02214, USA. swander@mgh.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe greater progression-free survival (PFS) improvements observed in first-line (1L) versus second-line (2L) CDK4/6 inhibitor (CDK4/6i) trials underpin current guideline recommendations establishing these agents as standard 1L therapy in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC). While earlier CDK4/6i use is associated with increased cumulative toxicity and costs, comparative survival data of earlier versus deferred use remain scarce.

methodsWe performed a systematic review and meta-analysis, searching PubMed, Embase, Cochrane, and conference proceedings for observational studies and randomized clinical trials (RCTs) including patients treated with first- and/or 2L CDK4/6i. Patients who received CDK4/6 inhibition as part of 1L therapy were included in the 1 L group, while those who did not receive CDK4/6i in the 1L setting and deferred it until the 2L setting were assigned to the 2 L group. Pooled analysis of Kaplan-Meier-derived individual patient data was conducted for PFS2, defined as time from randomization to progression on 2L therapy, and overall survival (OS). Both outcomes were measured from the start of 1L treatment to progression on 2L treatment for both 1L and 2L groups. Sensitivity analysis by study design was also conducted.

resultsNine studies (5 RCTs and 4 observational studies) comprising 7,602 patients with mBC were included. Of these, 6,475 (85.1%) received CDK4/6i in 1L, and 1,127 (14.8%) in the 2 L setting. Overall, 1L CDK4/6i therapy was associated with significantly longer PFS2 compared to 2L treatment (HR 2.08; 95%CI 1.90-2.27), a trend not observed in sensitivity analysis of RCTs alone (HR 1.10; 95%CI 0.94-1.30). No significant differences in OS were observed between 1L and 2L CDK4/6i regimens (HR 1.09; 95%CI 1.00-1.18), or in sensitivity analysis of only RCTs (HR 1.03; 95%CI 0.84-1.26).

conclusionThis extensive data pool suggests that deferring CDK4/6is to 2L may be associated with worse PFS2 but comparable OS when compared to early use in 1L, challenging the assumption that shifting therapies from 2L to 1L universally improves outcomes despite increased toxicity and costs.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Protein Kinase InhibitorsErb-b2 Receptor Tyrosine KinasesFemaleHumansNeoplasm MetastasisRandomized Controlled Trials as TopicReceptors, EstrogenReceptors, ProgesteroneTreatment OutcomeCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProtein Kinase InhibitorsReceptors, EstrogenReceptors, Progesterone

Identifiers

PMID40804745
PMCPMC12351955

What Socratic 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 Socratic graph.