Evidence map›Paper›PMID 29169877›Full record

Trial reportThe Lancet. Oncology2018

Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

Roy S Herbst, Mary W Redman, Edward S Kim, Thomas J Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad and 8 more

Open access · greenAbstract readClinical Trial, Phase IIIComparative StudyMulticenter Study
In one paragraph

Trial report in The Lancet. Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 5 pooled it
7.6field-weighted citation impact, top 2% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 5 syntheses or guidelines pooled it, 74 citations in OpenAlex.

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  7. EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 15 institutions in 1 country.

Roy S HerbstYale Cancer Center, Yale School of Medicine, New Haven, CT, USA. Electronic address: roy.herbst@yale.edu.
Mary W RedmanSouthwest Oncology Group (SWOG) Statistical Center and Clinical Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Edward S KimLevine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA.
Thomas J SemradUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Lyudmila BazhenovaMoores Cancer Center, University of California, San Diego, San Diego, CA, USA.
Gregory MastersChristiana Care Health Systems, Helen F Graham Cancer Center and Research Institute, Wilmington, DE, USA.
Kurt OettelWisconsin National Cancer Institute Community Oncology Research Program (NCORP), Gundersen Health System, LaCrosse, WI, USA.
Perry GuaglianoneHeartland Cancer Research NCORP, Cancer Care Specialists of Central Illinois, Decatur, IL, USA.
Christopher ReynoldsMichigan Cancer Research Consortium NCORP, St Joseph Mercy Health System, Ann Arbor, MI, USA.
Anand KarnadUniversity of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Susanne M ArnoldMarkey Cancer Center, University of Kentucky, Lexington, KY, USA.
Marileila Varella-GarciaDepartment of Medicine, Division of Medical Oncology, University of Colorado, Aurora, CO, USA.
James MoonSouthwest Oncology Group (SWOG) Statistical Center and Clinical Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Philip C MackUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Charles D BlankeSWOG Group Chair's Office, Oregon Health & Science University, Portland, OR, USA.
Fred R HirschDepartment of Medicine, Division of Medical Oncology, University of Colorado, Aurora, CO, USA.
Karen KellyUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
David R GandaraUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
UC Davis Comprehensive Cancer CenterUniversity of Colorado Anschutz Medical Campus · USCancer Research Center · USChristiana Care Health System · USFred Hutch Cancer Center · USHeartland Cancer Research · USLevine Cancer Institute · USMarkey Cancer Center · USMercy Health System · USNational Cancer Institute · USOregon Health & Science University · USThe University of Texas Health Science Center at San Antonio · USUniversity of California, Davis · USUniversity of California, San Diego · USYale Cancer Center · US

Funding

Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$167.6M
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
SWOG Statistics & Data Management Center complex - extension supplement for GY06U10CA180819 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Catherine M. Tangen · 2014 to 2026
$115.2M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Kaiser Permanente NCI National Community Oncology Research Program, NCORPUG1CA189821 · NCI · KAISER FOUNDATION RESEARCH INSTITUTE · PI Jennifer Marie Suga · 2014 to 2026
$44.4M
Heartland Cancer Research NCORPUG1CA189830 · NCI · DECATUR MEMORIAL HOSPITAL · PI Bryan A. Faller · 2014 to 2026
$40.9M
Southeast Clinical Oncology Research Consortium, Inc. (SCOR)UG1CA189858 · NCI · SOUTHEAST CLINICAL ONCOL RES CONSORTIUM · PI Judith O Hopkins, William J Irvin · 2014 to 2026
$38.8M
Michigan Cancer Research Consortium NCORPUG1CA189971 · NCI · SAINT JOSEPH MERCY HEALTH SYSTEM · PI Tareq Al baghdadi · 2014 to 2026
$36.6M
Cancer Research Consortium of West Michigan (CRCWM)UG1CA189860 · NCI · COREWELL HEALTH · PI KATHLEEN YOST BUTLER · 2014 to 2026
$29.1M
The Pacific Cancer Research Consortium (PCRC), an NCORP Community SiteUG1CA189953 · NCI · SWEDISH MEDICAL CENTER, FIRST HILL · PI Alison Katherine Conlin, Charles Drescher · 2014 to 2026
$27.4M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA046934NCI NIH HHS U10 CA180798NCI NIH HHS U10 CA180818NCI NIH HHS U10 CA180819NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180826NCI NIH HHS U10 CA180828NCI NIH HHS U10 CA180830NCI NIH HHS U10 CA180834NCI NIH HHS U10 CA180835NCI NIH HHS U10 CA180846NCI NIH HHS U10 CA180858NCI NIH HHS U10 CA180888NCI NIH HHS UG1 CA180830NCI NIH HHS UG1 CA189804NCI NIH HHS UG1 CA189808NCI NIH HHS UG1 CA189809NCI NIH HHS UG1 CA189817NCI NIH HHS UG1 CA189821NCI NIH HHS UG1 CA189822NCI NIH HHS UG1 CA189829NCI NIH HHS UG1 CA189830NCI NIH HHS UG1 CA189848NCI NIH HHS UG1 CA189854NCI NIH HHS UG1 CA189856NCI NIH HHS UG1 CA189858NCI NIH HHS UG1 CA189860NCI NIH HHS UG1 CA189872NCI NIH HHS UG1 CA189952NCI NIH HHS UG1 CA189953NCI NIH HHS UG1 CA189954NCI NIH HHS UG1 CA189957NCI NIH HHS UG1 CA189960NCI NIH HHS UG1 CA189971NCI NIH HHS UG1 CA189972NCI NIH HHS UG1 CA189997NCI NIH HHS UG1 CA233324
6 · The paper itself

Abstract

backgroundEGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

methodsWe did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m

findingsBetween Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control group in the EGFR FISH-positive subpopulation, progression-free survival did not differ between treatment groups (hazard ratio [HR] 0·92, 95% CI 0·75-1·12; p=0·40; median 5·4 months [95% CI 4·5-5·7] vs 4·8 months [3·9-5·5]). After 570 deaths in the cetuximab group and 593 in the control group, overall survival did not differ between the treatment groups in the entire study population (HR 0·93, 95% CI 0·83-1·04; p=0·22; median 10·9 months [95% CI 9·5-12·0] vs 9·2 months [8·7-10·3]). In the prespecified analysis of EGFR FISH-positive subpopulation with squamous cell histology, overall survival was significantly longer in the cetuximab group than in the control group (HR 0·58, 95% CI 0·36-0·86; p=0·0071), although progression-free survival did not differ between treatment groups in this subgroup (0·68, 0·46-1·01; p=0·055). Overall survival and progression-free survival did not differ among patients who were EGFR FISH non-positive with squamous cell histology (HR 1·04, 95% CI 0·78-1·40; p=0·77; and 1·02, 0·77-1·36; p=0·88 respectively) or patients with non-squamous histology regardless of EGFR FISH status (for EGFR FISH-positive 0·88, 0·68-1·14; p=0·34; and 0·99, 0·78-1·27; p=0·96; respectively; and for EGFR FISH non-positive 1·00, 0·85-1·17; p=0·97; and 1·03, 0·88-1·20; p=0·69; respectively). The most common grade 3-4 adverse events were decreased neutrophil count (210 [37%] in the cetuximab group vs 158 [25%] in the control group), decreased leucocyte count (103 [16%] vs 74 [20%]), fatigue (81 [13%] vs 74 [20%]), and acne or rash (52 [8%] vs one [<1%]). 59 (9%) patients in the cetuximab group and 31 (5%) patients in the control group had severe adverse events. Deaths related to treatment occurred in 32 (6%) patients in the cetuximab group and 13 (2%) patients in the control group.

interpretationAlthough this study did not meet its primary endpoints, prespecified subgroup analyses of patients with EGFR FISH-positive squamous-cell carcinoma cancers are encouraging and support continued evaluation of anti-EGFR antibodies in this subpopulation.

fundingNational Cancer Institute and Eli Lilly and Company.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCetuximabDisease-Free SurvivalDisease ProgressionErbB ReceptorsFemaleHumansIn Situ Hybridization, FluorescenceLung NeoplasmsMaleMexicoCarboplatinCetuximabEGFR protein, humanErbB ReceptorsPaclitaxel

Identifiers

PMID29169877
PMCPMC5847342
OpenAlexW2769988386

What OpenQuestion holds

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Registered trials

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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.