Evidence map›Paper›PMID 31276981›Full record

Trial reportEuropean journal of cancer (Oxford, England : 1990)2019

Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials.

M Martín, S Loibl, T Hyslop, J De la Haba-Rodríguez, B Aktas, C T Cirrincione, K Mehta, W T Barry, S Morales, L A Carey and 15 more

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in European journal of cancer (Oxford, England : 1990), 2019. 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 8 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 17% 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.

NCT00545077 phase3completednot on this map

Multicenter, Randomized Trial to Evaluate Efficacy and Safety of Bevacizumab in Combination With Endocrine Treatment vs Endocrine Alone, in Postmenopausal With Advanced or Metastatic Cancer With Indication of Hormonotherapy as First-line

TypeinterventionalSponsorSpanish Breast Cancer Research GroupRan2007 to 2014Enrolled380ConditionsBreast CancerArmsLetrozole, Bevacizumab, Fulvestrant
NCT00601900 phase3completednot on this map

Endocrine Therapy With or Without Anti-VEGF Therapy: A Randomized, Phase III Trial of Endocrine Therapy Alone or Endocrine Therapy Plus Bevacizumab (NSC 704865) for Women With Hormone Receptor-Positive Advanced Breast Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2008 to 2024Enrolled394ConditionsInvasive Breast Carcinoma, Recurrent Breast Carcinoma, Stage III Breast Cancer AJCC v6, Stage IV Breast Cancer AJCC v6 and v7ArmsBevacizumab, Laboratory Biomarker Analysis, Letrozole, Questionnaire Administration, Tamoxifen Citrate
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020
    Pooled it
  3. Trial
  4. Review
  5. Observational
  6. Review
  7. Article
  8. Article
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

25 authors at 12 institutions in 3 countries.

M MartínMedical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense Madrid, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, GEICAM Spanish Breast Cancer Group, Spain. Electronic address: mmartín@geicam.org.
S LoiblGBG (German Breast Group), Neu-Isenburg, Germany.
T HyslopAlliance Statistics and Data Center, Duke University, Durham, NC, USA.
J De la Haba-RodríguezOncology Department and Research Unit, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba Spain. Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, GEICAM Spanish Breast Cancer Group, Spain.
B AktasUniversity Women's Hospital Leipzig, Leipzig, Germany.
C T CirrincioneAlliance Statistics and Data Center, Duke University, Durham, NC, USA.
K MehtaGBG (German Breast Group), Neu-Isenburg, Germany.
W T BarryAlliance Statistics and Data Center, Dana-Farber/Partners Cancer Care, Boston, MA, USA.
S MoralesMedical Oncology, Hospital Arnau de Vilanova de Lérida, GEICAM Spanish Breast Cancer Group, Spain.
L A CareyUniversity of North Carolina, Chapel Hill, NC, USA.
J A Garcia-SaenzMedical Oncology, Instituto de Investigación Sanitaria del Hospital Clinico San Carlos (IdISSC) Madrid, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, GEICAM Spanish Breast Cancer Group, Spain.
A PartridgeDana-Farber/Partners CancerCare, Boston, MA, USA.
N Martinez-JañezMedical Oncology. Universitary Hospital Ramon y Cajal. GEICAM, Spanish Breast Cancer Group; Madrid, Spain.
O HahnAlliance Protocol Operations Office, University of Chicago, Chicago, IL, USA.
E WinerDana-Farber/Partners CancerCare, Boston, MA, USA.
A Guerrero-ZotanoMedical Oncology. Valencian Institute of Oncology. GEICAM Spanish Breast Cancer Group, Valencia, Spain.
C HudisAmerican Society of Clinical Oncology (ASCO), Alexandria, VA, USA.
M CasasGEICAM Spanish Breast Cancer Group, Madrid, Spain.
C Rodriguez-MartinGEICAM Spanish Breast Cancer Group, Madrid, Spain.
J FurlanettoGBG (German Breast Group), Neu-Isenburg, Germany.
E CarrascoGEICAM Spanish Breast Cancer Group, Madrid, Spain.
M N DicklerEli Lilly and Co. Indianapolis, IN, USA.
GEICAM Spanish Breast Cancer Group
GBG (German Breast Group)
Alliance for Clinical Trials in Oncology (Alliance)
GEICAM – Spanish Breast Cancer Group · ESGerman Breast group · DEAlliance Data (United States) · USDana-Farber/Harvard Cancer Center · USAmerican Society of Clinical Oncology · USEli Lilly (United States) · USHospital Arnau de Vilanova · ESInstituto de Investigación Sanitaria del Hospital Clínico San Carlos · ESInstituto Maimónides de Investigación Biomédica de Córdoba · ESUniversity Hospital Leipzig · DEUniversity of Chicago · USUniversity of North Carolina at Chapel Hill · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
Network Lead Academic Participating Site: Memorial Sloan Kettering Cancer CenterUG1CA233290 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CAROL AGHAJANIAN, Darren Feldman · 2019 to 2026
$10.2M
NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer CareUG1CA233180 · NCI · DANA-FARBER CANCER INST · PI Harold John Burstein · 2019 to 2026
$8.6M
NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer CareU10CA180867 · NCI · DANA-FARBER CANCER INST · PI BURSTEIN, HAROLD JOHN, KIBEL, ADAM S · 2014 to 2018
$6.2M
UNC Lead Academic Participating SiteUG1CA233373 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CAREY, LISA A, DEES, ELIZABETH CLAIRE · 2019 to 2025
$3.5M
NCTN Lead Academic Participating Sites ApplicationU10CA180838 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CAREY, LISA A · 2014 to 2018
$2.8M
NCI NIH HHS P30 CA008748NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180838NCI NIH HHS U10 CA180867NCI NIH HHS U10 CA180882NCI NIH HHS UG1 CA233180NCI NIH HHS UG1 CA233290NCI NIH HHS UG1 CA233373
6 · The paper itself

Abstract

backgroundRandomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results. PATIENTS AND

methodsWe pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria.

resultsThe pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33).

conclusionThe addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity. TRIALS REGISTRATION: ClinicalTrial.Gov NCT00545077 and NCT00601900.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBone NeoplasmsBreast NeoplasmsEvaluation Studies as TopicFemaleFollow-Up StudiesFulvestrantHumansLetrozoleMiddle AgedNeoplasm Recurrence, LocalPrognosisBevacizumabFulvestrantLetrozoleReceptors, EstrogenReceptors, ProgesteroneTamoxifenAdvanced breast cancerBevacizumabEndocrine therapyPooled-analysis

Identifiers

PMID31276981
PMCPMC6718694
OpenAlexW2953682493

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.