Evidence map›Paper›PMID 30206110›Full record

Trial reportCancer discovery2018

The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial.

Ben O'Leary, Rosalind J Cutts, Yuan Liu, Sarah Hrebien, Xin Huang, Kerry Fenwick, Fabrice André, Sibylle Loibl, Sherene Loi, Isaac Garcia-Murillas and 3 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Cancer discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04985266 (A Randomised Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer), which is not on this map. Cited by 397 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
397citing papers in PubMed, 4 pooled it
42.0field-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.

NCT04985266 phase2recruitingnot on this mapstarted 2022, after this paper: background citation

A Randomised Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer

TypeinterventionalSponsorRoyal Marsden NHS Foundation TrustRan2022 to 2030Enrolled1,100ConditionsER+ Breast Cancer, HER2-negative Breast CancerArmsPalbociclib 125Mg Tab, Fulvestrant injection, Tamoxifen, Letrozole, Exemestane
3 · Its place in the literature

Who cites it

397 citing papers in PubMed, 4 syntheses or guidelines pooled it, 656 citations in OpenAlex.

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  3. Multilevel Mechanisms of Cancer Drug Resistance.International journal of molecular sciences · 2024
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337 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 5 countries.

Ben O'LearyBreast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom.
Rosalind J CuttsBreast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom.
Yuan LiuPfizer, New York, New York.
Sarah HrebienBreast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom.
Xin HuangPfizer, New York, New York.
Kerry FenwickTumour Profiling Unit, The Institute of Cancer Research, London, United Kingdom.
Fabrice AndréDepartment of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Sibylle LoiblGerman Breast Group, Neu-Isenburg, Germany.
Sherene LoiDivision of Research and Cancer Medicine, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID 0000-0001-6137-9171
Isaac Garcia-MurillasBreast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0001-8183-7969
Massimo CristofanilliRobert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois.
Cynthia Huang BartlettPfizer, New York, New York.
Nicholas C TurnerBreast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom. Nick.Turner@icr.ac.uk.
Breast Cancer Now · GBThe Fertilizer Institute · USGerman Breast group · DEInstitute of Cancer Research · GBInstitut Gustave Roussy · FRPeter MacCallum Cancer Centre · AURobert H. Lurie Comprehensive Cancer Center of Northwestern University

Funding

Cancer Research UK C1491/A15955Department of HealthMedical Research Council MR/N002121/1
6 · The paper itself

Abstract

CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced estrogen receptor-positive breast cancer. Mechanisms of CDK4/6 inhibitor resistance have been described preclinically, with limited evidence from clinical samples. We conducted paired baseline and end-of-treatment circulating tumor DNA sequencing from 195 patients in the PALOMA-3 randomized phase III trial of palbociclib plus fulvestrant versus placebo plus fulvestrant. We show that clonal evolution occurs frequently during treatment, reflecting substantial subclonal complexity in breast cancer that has progressed after prior endocrine therapy.

Indexed as

Clonal EvolutionAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodDrug Resistance, NeoplasmEstrogen Receptor alphaFemaleFollow-Up StudiesFulvestrantHumansMutationPiperazinesPrognosisPyridinesBiomarkers, TumorESR1 protein, humanEstrogen Receptor alphaFulvestrantpalbociclibPiperazinesPyridines

Identifiers

PMID30206110
PMCPMC6368247
OpenAlexW2892043300

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.