Evidence map›Paper›PMID 24615500›Full record

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

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

H S Rugo, K I Pritchard, M Gnant, S Noguchi, M Piccart, G Hortobagyi, J Baselga, A Perez, M Geberth, T Csoszi and 9 more

Registry-linked trialOpen access · bronzeAbstract readRandomized 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 NCT00863655 (A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole), which is not on this map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
16.9field-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.

NCT00863655 phase3completednot on this map

A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2014Enrolled724ConditionsBreast CancerArmsEverolimus, Exemestane, Everolimus Placebo
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.

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  5. Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 15 institutions in 8 countries.

H S RugoUniversity of California, San Francisco Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, USA. Electronic address: hrugo@medicine.ucsf.edu.
K I PritchardSunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Canada.
M GnantDepartment of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
S NoguchiDepartment of Breast and Endocrine Surgery, Osaka University, Osaka, Japan.
M PiccartInstitut Jules Bordet, Brussels, Belgium.
G HortobagyiThe University of Texas MD Anderson Cancer Center, Houston.
J BaselgaMemorial Sloan-Kettering Cancer Center, New York.
A PerezMemorial Cancer Institute, Hollywood, USA.
M GeberthPraxisklinic am Rosengarten Mannheim, Schwerpunktpraxis für Gynaekologische Onkologie, Mannheim, Germany.
T CsosziDepartment of Medical Oncology, Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Szolnok, Hungary.
E ChouinardCambridge Memorial Hospital, Cambridge, Canada.
V SrimuninnimitSiriraj Hospital, Mahidol University, Bangkok.
P PuttawibulSongklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand.
J EakleFlorida Cancer Specialists, Ft Myers.
W FengNovartis Pharmaceuticals Corporation, East Hanover, USA.
H BaulyNovartis Pharma AG, Basel, Switzerland.
M El-HashimyNovartis Pharmaceuticals Corporation, East Hanover, USA.
T TaranNovartis Pharmaceuticals Corporation, East Hanover, USA.
H A BurrisSarah Cannon Research Institute, Nashville, USA.
Novartis (United States) · USCambridge Memorial Hospital · CAFlorida Cancer Specialists & Research Institute · USInstitut Jules Bordet · BEMedical University of Vienna · ATMemorial Sloan Kettering Cancer Center · USNovartis (Switzerland) · CHOsaka University · JPPraxis für Hämatologie und Onkologie · DESarah Cannon · USSiriraj Hospital · THSongklanagarind Hospital · THThe University of Texas MD Anderson Cancer Center · USUCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of Toronto · CA

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study. PATIENTS AND

methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.

resultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).

conclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education. TRIAL REGISTRATION NUMBER: NCT00863655.

Indexed as

AdultAgedAged, 80 and overBreast NeoplasmsDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsEverolimusFemaleHumansMiddle AgedNeoplasm StagingPostmenopauseSirolimusTOR Serine-Threonine KinasesEverolimusMTOR protein, humanSirolimusTOR Serine-Threonine Kinasesadvanced breast cancereverolimusmammalian target of rapamycin (mTOR)safety

Identifiers

PMID24615500
PMCPMC3969554
OpenAlexW2109381544

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.