Evidence mapPaperPMID 40796258Full record

SynthesisJNCI cancer spectrum2025

Comparative efficacy between real-world and randomized studies of palbociclib+endocrine therapy in HR-positive/HER2-negative metastatic breast cancer: systematic review and meta-analysis.

Francesco Schettini, Sabrina Nucera, Giuseppe Di Grazia, Fabiola Giudici, Carla Strina, Manuela Milani, Richard Tancredi, Benedetta Conte, Carmen Criscitiello, Mario Giuliano and 11 more

Abstract readSystematic ReviewMeta-AnalysisComparative Study
In one paragraph

Synthesis in JNCI cancer spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Francesco SchettiniTranslational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0000-0001-6561-1919
Sabrina NuceraTranslational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0009-0004-7092-1785
Giuseppe Di GraziaTranslational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0009-0001-6147-9655
Fabiola GiudiciCancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.ORCID 0000-0002-4160-3479
Carla StrinaMultidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy.
Manuela MilaniMultidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy.
Richard TancrediMultidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy.
Benedetta ConteTranslational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0000-0003-4720-2497
Carmen CriscitielloDepartment of Oncology and Hemato-Oncology, University of Milano, Milan, Italy.ORCID 0000-0001-9064-0113
Mario GiulianoDepartment of Clinical Medicine and Surgery, University Federico II, Naples, Italy.ORCID 0000-0003-0835-3153
Matteo LambertiniDepartment of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.ORCID 0000-0003-1797-5296
Rodrigo Sánchez-BayonaDepartment of Medical Oncology, Hospital Universitario, Madrid, Spain.ORCID 0000-0002-5255-6620
Tomás PascualTranslational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.ORCID 0000-0001-8431-3183
Grazia ArpinoDepartment of Clinical Medicine and Surgery, University Federico II, Naples, Italy.ORCID 0000-0002-4074-2530
Lucia Del MastroDepartment of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.ORCID 0000-0002-9546-5841
Paolo VigneriDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.ORCID 0000-0002-5943-6066
Massimo CristofanilliDepartment of Medicine, Division of Hematology-Oncology, Weill Cornell Medicine, New York, NY, United States.ORCID 0000-0002-4194-7175
Hope S RugoDepartment of Medicine (Hematology/Oncology), University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, United States.ORCID 0000-0001-6710-4814
Alessandra GennariDepartment of Translational Medicine, University of Piemonte Orientale, Novara, Italy.ORCID 0000-0002-0928-2281
Giuseppe CuriglianoDepartment of Oncology and Hemato-Oncology, University of Milano, Milan, Italy.ORCID 0000-0003-1781-2518
Daniele GeneraliMultidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, Cremona, Italy.ORCID 0000-0003-2480-3855

Funding

Instituto de Salud Carlos III ISCIII, JR24/00024
6 · The paper itself

Abstract

backgroundCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.

methodsWe conducted a systematic review and meta-analysis of RW studies on HR+/HER2- MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs' 95% confidence intervals (CIs). Similar criteria applied to pooled hazard ratios (HRs) of PFS/OS for palbociclib+AI vs AI in visceral/nonvisceral subgroups.

resultsTwelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95% CI = 19.5 to 31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI = 20.2 to 27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95% CI = 11.6 to 28.5) exceeded PALOMA-3 (11.2, 95% CI = 9.5 to 12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95% CI = 6.3 to 15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95% CI = 49.1 to 53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95% CI = 37.5 to 53.8). WMOS (49.1 months, 95% CI = 49.1 to 53.3) was slightly lower than RCTs (53.7, 95% CI = 37.5 to 53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in nonvisceral disease.

conclusionsRW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsPiperazinesPyridinesAromatase InhibitorsCyclin-Dependent Kinase 4Erb-b2 Receptor Tyrosine KinasesFemaleFulvestrantHumansProgression-Free SurvivalProtein Kinase InhibitorsRandomized Controlled Trials as TopicReceptors, EstrogenReceptors, ProgesteroneAromatase InhibitorsCyclin-Dependent Kinase 4ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesFulvestrantpalbociclibPiperazinesProtein Kinase InhibitorsPyridinesReceptors, EstrogenReceptors, Progesterone

Identifiers

PMID40796258
PMCPMC12413244

What Socratic holds

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Registered trials

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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.