Evidence map›Paper›PMID 29497091›Full record

Trial reportNature communications2018

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

Ben O'Leary, Sarah Hrebien, James P Morden, Matthew Beaney, Charlotte Fribbens, Xin Huang, Yuan Liu, Cynthia Huang Bartlett, Maria Koehler, Massimo Cristofanilli and 3 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 242 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed, 3 pooled it
–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.

NCT04920708 phase2active not recruitingnot on this mapstarted 2022, after this paper: background citation

Randomised Open-label Phase II Study of Induction Standard of Care Fulvestrant and CDK4/6 Inhibition With the Addition of Ipatasertib in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression

TypeinterventionalSponsorRoyal Marsden NHS Foundation TrustRan2022 to 2027Enrolled57ConditionsMetastatic Breast Cancer, ER+ Breast Cancer, Advanced Breast CancerArmsIpatasertib 300mg, Fulvestrant 500g, Palbociclib 75mg-125mg, CDK4/6 Inhibitor
NCT05644457 recruitingnot on this mapstarted 2022, after this paper: background citation

Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck

TypeobservationalSponsorRoyal Marsden NHS Foundation TrustRan2022 to 2026Enrolled50ConditionsHead and Neck CancerArmsCirculating tumour DNA dynamics
3 · Its place in the literature

Who cites it

242 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  16. Cancers · 2026
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182 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.

Ben O'LearyBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0002-1092-9169
Sarah HrebienBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.
James P MordenThe Institute of Cancer Research Clinical Trials and Statistics Unit, London, SM2 5NG, UK.
Matthew BeaneyBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.
Charlotte FribbensBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.
Xin HuangPfizer, 235 E 42nd St, New York, NY, 10017, USA.
Yuan LiuPfizer, 235 E 42nd St, New York, NY, 10017, USA.
Cynthia Huang BartlettPfizer, 235 E 42nd St, New York, NY, 10017, USA.
Maria KoehlerPfizer, 235 E 42nd St, New York, NY, 10017, USA.
Massimo CristofanilliRobert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 675 N St. Clair, Chicago, IL, 60611, USA.
Isaac Garcia-MurillasBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.
Judith M BlissThe Institute of Cancer Research Clinical Trials and Statistics Unit, London, SM2 5NG, UK.
Nicholas C TurnerBreast Cancer Now Research Centre, The Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK. nicholas.turner@icr.ac.uk.

Funding

Cancer Research UK 15955Medical Research Council MR/N002121/1
6 · The paper itself

Abstract

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

Indexed as

Antineoplastic AgentsBreast NeoplasmsCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase 6Disease-Free SurvivalEstradiolFemaleFulvestrantHumansPiperazinesPyridinesReceptors, EstrogenAntineoplastic AgentsCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase 6EstradiolFulvestrantpalbociclibPIK3CA protein, humanPiperazinesPyridinesReceptors, Estrogen

Identifiers

PMID29497091
PMCPMC5832789

What OpenQuestion holds

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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.