Evidence map›Paper›PMID 34933868›Full record

SynthesisBMJ (Clinical research ed.)2021

Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis.

Fabio Conforti, Laura Pala, Isabella Sala, Chiara Oriecuia, Tommaso De Pas, Claudia Specchia, Rossella Graffeo, Eleonora Pagan, Paola Queirolo, Elisabetta Pennacchioli and 4 more

Open access · hybridAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ (Clinical research ed.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 8 pooled it
7.5field-weighted citation impact, top 1% 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

106 citing papers in PubMed, 8 syntheses or guidelines pooled it, 133 citations in OpenAlex.

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  4. The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective.European journal of nuclear medicine and molecular imaging · 2024
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  10. Computationally Derived Spatial Immune Signature Identifies Trastuzumab Responders in HER2+ Breast Cancer: NSABP B-41 Clinical Trial Validation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  11. Accelerating Drug Development in Hormone-Naïve Prostate Cancer through Multimodal Therapy Strategies: The MetaCURE Phase 2 Randomized Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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46 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

14 authors at 7 institutions in 3 countries.

Fabio ConfortiDivision of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.ORCID 0000-0002-6233-0502
Laura PalaDivision of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Isabella SalaDepartment of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
Chiara OriecuiaDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Tommaso De PasDivision of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Claudia SpecchiaDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Rossella GraffeoBreast Unit of Southern Switzerland, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Eleonora PaganDepartment of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
Paola QueiroloDivision of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Elisabetta PennacchioliDivision of Melanoma, Sarcomas and Rare Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Marco ColleoniDivision of Medical Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Giuseppe VialeDepartment of Pathology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Vincenzo BagnardiDepartment of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
Richard D GelberMedical School, Harvard T H Chan School of Public Health, and Frontier Science and Technology Research Foundation, Boston, MA, USA.
European Institute of Oncology · ITUniversity of Milano-Bicocca · ITUniversity of Brescia · ITFrontier Science & Technology Research Foundation · USInstitute of Oncology Research · CHIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.

designSystematic review and meta-analysis. DATA SOURCES: Medline, Embase, and Scopus to 1 December 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors. DATA EXTRACTION AND SYNTHESIS: Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival.

methodsA weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R

results54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R

conclusionA lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

Indexed as

BiomarkersBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansNeoadjuvant TherapyRandomized Controlled Trials as TopicBiomarkers

Identifiers

PMID34933868
PMCPMC8689398
OpenAlexW4200089627

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.