Evidence mapPaperPMID 32407488Full record

SynthesisJournal of the National Cancer Institute2020

Overall Survival of CDK4/6-Inhibitor-Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis.

Francesco Schettini, Fabiola Giudici, Mario Giuliano, Massimo Cristofanilli, Grazia Arpino, Lucia Del Mastro, Fabio Puglisi, Sabino De Placido, Ida Paris, Pietro De Placido and 10 more

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 6 pooled it
8.2field-weighted citation impact, top 2% of its field
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

64 citing papers in PubMed, 6 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Pooled it
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4 more citing papers are in PubMed but not listed here.

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

20 authors at 17 institutions in 4 countries.

Francesco SchettiniDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Fabiola GiudiciDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Mario GiulianoDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Massimo CristofanilliNorthwestern University Clinical and Translational Sciences Institute (NUCATS), Northwestern University, Chicago, IL, USA.
Grazia ArpinoDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Lucia Del MastroOspedale Policlinico San Martino-IRCCS, Genova, Italy.
Fabio PuglisiDepartment of Medicine, University of Udine, Udine, Italy.
Sabino De PlacidoDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Ida ParisDivision of Gynecologic Oncology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Pietro De PlacidoDepartment of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Sergio VenturiniDepartment of Management, University of Turin, Turin, Italy.
Michelino De LaurentisBreast Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Naples, Italy.
PierFranco ConteDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Dejan JuricMassachusetts General Hospital Cancer Center, Boston, MA, USA.
Antonio Llombart-CussacSOLTI Breast Cancer Research Group, Barcelona, Spain.
Lajos PusztaiDepartment of Internal Medicine, Section of Medical Oncology, Yale, Cancer Centre, Yale University, School of Medicine, New Haven, CT, USA.
Aleix PratTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Guy JerusalemCentre Hospitalier Universitaire de Liège and Liège University, Liège, Belgium.
Angelo Di Leo"Sandro Pitigliani" Medical Oncology Department, Hospital of Prato, Prato, Italy.
Daniele GeneraliDepartment of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
University of Naples Federico II · ITUniversity of Padua · ITAgostino Gemelli University Polyclinic · ITBaylor College of Medicine · USCentre Hospitalier Universitaire de Liège · BEConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESHospital Arnau de Vilanova · ESHospital Clínic de Barcelona · ESHospital of Prato · ITIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · ITMassachusetts General Hospital · USNorthwestern University · USOspedale Policlinico San Martino · ITUniversity of Trieste · ITUniversity of Turin · ITUniversity of Udine · ITYale Cancer Center · US

Funding

Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

backgroundCyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups.

methodsWe conducted a systematic literature search to select all available phase II or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. Subgroup analysis was performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP).

resultsSix studies were included in our analyses (3421 patients). A clear OS benefit was observed in patients without (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.54 to 0.85, I2 = 0.0%) and with visceral involvement (HR = 0.76, 95% CI = 0.65 to 0.89, I2 = 0.0%), with at least 3 metastatic sites (HR = 0.75, 95% CI = 0.60 to 0.94, I2 = 11.6%), in an endocrine-resistant (HR = 0.79, 95% CI = 0.67 to 0.93, I2 = 0.0%) and sensitive subset (HR = 0.73, 95% CI = 0.61 to 0.88, I2 = 0.0%), for younger than 65 years (HR = 0.80, 95% CI = 0.67 to 0.95, I2 = 0.0%) and 65 years or older (HR = 0.71, 95% CI = 0.53 to 0.95, I2 = 44.4%), in postmenopausal (HR = 0.76, 95% CI = 0.67 to 0.86, I2 = 0.0%) and pre- or perimenopausal setting (HR = 0.76, 95% CI = 0.60 to 0.96, I2 = 0.0%) as well as in chemotherapy-naïve patients (HR = 0.72, 95% CI = 0.55 to 0.93, I2 = 0.0%).

conclusionsCDK4/6-inhibitors + ET combinations compared with ET alone improve OS independent of age, menopausal status, endocrine sensitiveness, and visceral involvement and should be preferred as upfront therapy instead of endocrine monotherapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6FemaleHumansLetrozoleNeoplasm MetastasisPiperazinesProtein Kinase InhibitorsPyridinesRandomized Controlled Trials as TopicCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6LetrozolepalbociclibPiperazinesProtein Kinase InhibitorsPyridines

Identifiers

PMID32407488
PMCPMC7669227
OpenAlexW3025126564

What Socratic holds

Textmetadata
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.