Evidence map›Paper›PMID 24685829›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2014

Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA.

S M Swain, J Baselga, D Miles, Y-H Im, C Quah, L F Lee, J Cortés

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00567190 (A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer), which is not on this map. Cited by 123 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed, 6 pooled it
15.7field-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.

NCT00567190 phase3completednot on this map

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer

TypeinterventionalSponsorGenentech, Inc.Ran2008 to 2018Enrolled808ConditionsMetastatic Breast CancerArmsPertuzumab, Placebo, Trastuzumab, Docetaxel
3 · Its place in the literature

Who cites it

123 citing papers in PubMed, 6 syntheses or guidelines pooled it, 230 citations in OpenAlex.

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  12. Chinese Society of Clinical Oncology breast cancer expert consensus on the diagnosis and treatment of breast cancer brain metastasis (2025).Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
    Review
  13. Therapeutics and toxicity management of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
    Review
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63 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

7 authors at 5 institutions in 4 countries.

S M SwainWashington Cancer Institute, MedStar Washington Hospital Center, Washington sandra.m.swain@medstar.net.
J BaselgaMemorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, USA.
D MilesMount Vernon Cancer Centre, Middlesex, UK.
Y-H ImDivision of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
C QuahGenentech, Inc., South San Francisco, USA.
L F LeeGenentech, Inc., South San Francisco, USA.
J CortésVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
MedStar Washington Hospital Center · USMemorial Hospital · USMount Vernon Cancer Centre · GBSungkyunkwan University · KRVall d'Hebron Hospital Universitari · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundResults from the phase III trial CLEOPATRA in human epidermal growth factor receptor 2-positive first-line metastatic breast cancer demonstrated significant improvements in progression-free and overall survival with pertuzumab, trastuzumab, and docetaxel over placebo, trastuzumab, and docetaxel. We carried out exploratory analyses of the incidence and time to development of central nervous system (CNS) metastases in patients from CLEOPATRA. PATIENTS AND

methodsPatients received pertuzumab/placebo: 840 mg in cycle 1, then 420 mg; trastuzumab: 8 mg/kg in cycle 1, then 6 mg/kg; docetaxel: initiated at 75 mg/m(2). Study drugs were administered i.v. every 3 weeks. The log-rank test was used for between-arm comparisons of time to CNS metastases as first site of disease progression and overall survival in patients with CNS metastases as first site of disease progression. The Kaplan-Meier approach was used to estimate median time to CNS metastases as first site of disease progression and median overall survival.

resultsThe incidence of CNS metastases as first site of disease progression was similar between arms; placebo arm: 51 of 406 (12.6%), pertuzumab arm: 55 of 402 (13.7%). Median time to development of CNS metastases as first site of disease progression was 11.9 months in the placebo arm and 15.0 months in the pertuzumab arm; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.39-0.85, P = 0.0049. Overall survival in patients who developed CNS metastases as first site of disease progression showed a trend in favor of pertuzumab, trastuzumab, and docetaxel; HR = 0.66, 95% CI 0.39-1.11. Median overall survival was 26.3 versus 34.4 months in the placebo and pertuzumab arms, respectively. Treatment comparison of the survival curves was not statistically significant for the log-rank test (P = 0.1139), but significant for the Wilcoxon test (P = 0.0449).

conclusionsWhile the incidence of CNS metastases was similar between arms, our results suggest that pertuzumab, trastuzumab, and docetaxel delays the onset of CNS disease compared with placebo, trastuzumab, and docetaxel. CLINICALTRIALSGOV: NCT00567190.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCentral Nervous System NeoplasmsDocetaxelDouble-Blind MethodErb-b2 Receptor Tyrosine KinasesFemaleHumansIncidenceKaplan-Meier EstimateMiddle AgedProportional Hazards ModelsTaxoidsAntibodies, Monoclonal, HumanizedDocetaxelERBB2 protein, humanErb-b2 Receptor Tyrosine KinasespertuzumabTaxoidsTrastuzumabcentral nervous systemHER2metastatic breast cancerpertuzumabtrastuzumab

Identifiers

PMID24685829
PMCPMC4037862
OpenAlexW2109176076

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.