Evidence map›Paper›PMID 27964843›Full record

Trial reportThe Lancet. Oncology2017

Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study.

Stephen J Luen, Roberto Salgado, Stephen Fox, Peter Savas, Jennifer Eng-Wong, Emma Clark, Astrid Kiermaier, Sandra M Swain, Jose Baselga, Stefan Michiels and 1 more

Erratum issued 2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 160 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 6 pooled it
15.4field-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
NCT04895761 phase1active not recruitingnot on this mapstarted 2021, after this paper: background citation

Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

TypeinterventionalSponsorProvidence Health & ServicesRan2021 to 2026Enrolled6ConditionsBreast CancerArmsDPX-Survivac, Letrozole 2.5mg, Cyclophosphamide 50mg, XRT 10Gy x2
3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 6 syntheses or guidelines pooled it, 285 citations in OpenAlex.

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  17. Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 8 institutions in 6 countries.

Stephen J LuenPeter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
Roberto SalgadoDepartment of Pathology, GZA-Hospitals, Antwerp, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Stephen FoxPeter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
Peter SavasPeter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
Jennifer Eng-WongGenentech, South San Francisco, CA, USA.
Emma ClarkRoche Products, Welwyn, UK.
Astrid KiermaierOncology Biomarker Development, Roche, Basel, Switzerland.
Sandra M SwainLombardi Comprehensive Cancer Centre, Georgetown University, Washington, DC, USA.
Jose BaselgaMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Stefan MichielsService de Biostatistique et d'Epidémiologie, Gustave Roussy, CESP, Inserm U1018, Université-Paris Sud, Université Paris-Saclay, Villejuif, France.
Sherene LoiPeter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia. Electronic address: sherene.loi@petermac.org.
Peter MacCallum Cancer Centre · AUUniversity of Melbourne · AUGeorgetown University · USGZA Ziekenhuizen Campus Sint-Augustinus · BEInserm · FRMemorial Sloan Kettering Cancer Center · USRoche (Switzerland) · CHRoche (United Kingdom) · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundHigh quantities of tumour-infiltrating lymphocytes (TILs) in primary HER2-positive breast cancer are associated with improved prognosis and response to therapy. We aimed to investigate the prognostic role of host antitumour immunity as represented by baseline quantities of TILs in patients with advanced HER2-positive breast cancer treated with either pertuzumab or placebo in addition to trastuzumab and docetaxel.

methodsCLEOPATRA was a randomised phase 3 study comparing the addition of either pertuzumab or placebo to first-line therapy with trastuzumab and docetaxel for patients with locally recurrent, unresectable, or metastatic HER2-positive breast cancer. We assessed the quantity of stromal TILs in prospectively collected tumour samples and investigated their association with progression-free survival, overall survival, clinicopathological characteristics, and pertuzumab treatment. We estimated hazard ratios (HR) and 95% CIs with multivariate Cox regression models fitting stromal TILs as a continuous variable (per 10% increment). The CLEOPATRA trial is registered with ClinicalTrials.gov, number NCT00567190.

findingsTumour samples from 678 (84%) of 808 participants were evaluable for TILs, including 519 (77%) archival samples, 155 (23%) freshly obtained samples (collected 45 days or fewer before randomisation), and four samples of unknown archival status. Median follow-up was 50 months (IQR 41-54) for progression-free survival and 51 months (IQR 46-57) for overall survival. 519 progression-free survival events occurred and 358 patients died. The median TIL value was 10% (IQR 5-30). Freshly obtained tumour samples had significantly lower TIL values than did archival samples (10·00% [95% CI 5·00-20·00] vs 15·00% [5·00-35·00]; p=0·00036). We detected no significant association between TIL values and progression-free survival (adjusted HR 0·95, 95% CI 0·90-1·00, p=0·063). However, for overall survival, each 10% increase in stromal TILs was significantly associated with longer overall survival (adjusted HR 0·89, 95% CI 0·83-0·96, p=0·0014). The treatment effect of pertuzumab did not differ significantly by stromal TIL value for either progression-free survival (p

interpretationIn patients with advanced HER2-positive breast cancer treated with docetaxel, trastuzumab, and pertuzumab or placebo, higher TIL values are significantly associated with improved overall survival, suggesting that the effect of antitumour immunity extends to the advanced setting. Future clinical studies in this cancer subtype should consider TILs as a stratification factor and investigate whether therapies that can augment immunity could potentially further improve survival.

fundingF Hoffmann-La Roche-Genentech and the Breast Cancer Research Foundation.

Indexed as

AdolescentAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDocetaxelDouble-Blind MethodErb-b2 Receptor Tyrosine KinasesFemaleFollow-Up StudiesHumansLymphatic MetastasisLymphocytes, Tumor-InfiltratingMiddle AgedAntibodies, Monoclonal, HumanizedBiomarkers, TumorDocetaxelErb-b2 Receptor Tyrosine KinasespertuzumabTaxoidsTrastuzumab

Identifiers

PMID27964843
PMCPMC5477653
OpenAlexW2559858344

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.