Evidence map›Paper›PMID 29420467›Full record

Trial reportNature2018

HER kinase inhibition in patients with HER2- and HER3-mutant cancers.

David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger and 37 more

Erratum issued Registry-linked trialAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature, 2018. 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 trial NCT01953926 (An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations), which is not on this map. Cited by 453 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
453citing papers in PubMed, 5 pooled it
35.5field-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.

NCT01953926 phase2terminatednot on this map

An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations

TypeinterventionalSponsorPuma Biotechnology, Inc.Ran2013 to 2023Enrolled582ConditionsSolid Tumors Harboring Somatic HER2 or EGFR Exon 18 MutationsArmsNeratinib, Fulvestrant, Trastuzumab, Paclitaxel
3 · Its place in the literature

Who cites it

453 citing papers in PubMed, 5 syntheses or guidelines pooled it, 769 citations in OpenAlex.

  1. Guideline
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  15. Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4).Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023
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393 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors at 11 institutions in 3 countries.

David M HymanMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Sarina A Piha-PaulUniversity of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
Helen WonMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Jordi RodonVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Cristina SauraVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Geoffrey I ShapiroDana-Faber Cancer Institute, Boston, Massachusetts, USA.
Dejan JuricMassachusetts Hospital Cancer Center, Boston, Massachusetts, USA.
David I QuinnUSC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Victor MorenoSTART Madrid Fundación Jímenez Díaz, Madrid, Spain.
Bernard DogerSTART Madrid Fundación Jímenez Díaz, Madrid, Spain.
Ingrid A MayerVanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Valentina BoniSTART Madrid, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain.
Emiliano CalvoSTART Madrid, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain.
Sherene LoiPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Albert C LockhartWashington University in St. Louis School of Medicine, St Louis, Missouri, USA.
Joseph P ErinjeriMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Maurizio ScaltritiMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Gary A UlanerMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Juber PatelMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Jiabin TangMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Hannah BeerMemorial Sloan Kettering Cancer Center, New York, New York, USA.
S Duygu SelcukluMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Aphrothiti J HanrahanMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Nancy BouvierMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Myra MelcerMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Rajmohan MuraliMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Alison M SchramMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Lillian M SmythMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Komal JhaveriMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Bob T LiMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Alexander DrilonMemorial Sloan Kettering Cancer Center, New York, New York, USA.
James J HardingMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Gopa IyerMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Barry S TaylorMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Michael F BergerMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Richard E CutlerPuma Biotechnology Inc., Los Angeles, California, USA.
Feng XuPuma Biotechnology Inc., Los Angeles, California, USA.
Anna ButturiniPuma Biotechnology Inc., Los Angeles, California, USA.
Lisa D EliPuma Biotechnology Inc., Los Angeles, California, USA.
Grace MannPuma Biotechnology Inc., Los Angeles, California, USA.
Cynthia FarrellPuma Biotechnology Inc., Los Angeles, California, USA.
Alshad S LalaniPuma Biotechnology Inc., Los Angeles, California, USA.
Richard P BrycePuma Biotechnology Inc., Los Angeles, California, USA.
Carlos L ArteagaVanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Funda Meric-BernstamUniversity of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
José BaselgaMemorial Sloan Kettering Cancer Center, New York, New York, USA.
David B SolitMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Memorial Sloan Kettering Cancer Center · USPuma Biotechnology (United States) · USHospital Universitario Fundación Jiménez Díaz · ESThe University of Texas MD Anderson Cancer Center · USVanderbilt-Ingram Cancer CenterDana-Farber Cancer Institute · USPeter MacCallum Cancer Centre · AUUSC Norris Comprehensive Cancer Center · USVall d'Hebron Hospital Universitari · ESVall d'Hebron Institute of OncologyWashington University in St. Louis · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
Investigational Cancer Therapeutics Training Program (ICTTP)T32CA009207 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Omar Abdel-Wahab, Alexander Drilon · 1985 to 2026
$13.7M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
Summer research experiences for medical students supervised by faculty mentorsR25CA020449 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Charlotte Eielson Ariyan · 1985 to 2026
$6.2M
ERBB2 TARGETED ANTITUMOR STRATEGIES IN BREAST CANCERR01CA080195 · NCI · VANDERBILT UNIVERSITY · PI ARTEAGA, CARLOS L · 1999 to 2014
$3.9M
Understanding Long Tail Driver Mutations in CancerR01CA204749 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SCHULTZ, NIKOLAUS · 2017 to 2021
$2.0M
Informatics to enable routine personalized cancer therapyU01CA180964 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BERNSTAM, ELMER V., MERIC-BERNSTAM, FUNDA · 2013 to 2015
$964k
NCATS NIH HHS UL1 TR000371NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA098131NCI NIH HHS R01 CA080195NCI NIH HHS R01 CA204749NCI NIH HHS R25 CA020449NCI NIH HHS T32 CA009207NCI NIH HHS U01 CA180964NIH HHS 1U01 CA180964NIH HHS R01 CA80195
6 · The paper itself

Abstract

Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.

Indexed as

MutationAdultAgedAged, 80 and overAllelesAntineoplastic AgentsCohort StudiesErb-b2 Receptor Tyrosine KinasesFemaleHumansMaleMiddle AgedMolecular Targeted TherapyMutation, MissenseNeoplasmsProtein Kinase InhibitorsAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanneratinibProtein Kinase InhibitorsQuinolinesReceptor, ErbB-3

Identifiers

PMID29420467
PMCPMC5808581
OpenAlexW2785610956

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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.