Evidence map›Paper›PMID 40473450›Full record

Trial reportLancet (London, England)2025

Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study.

Alice P Chen, Geraldine O'Sullivan Coyne, Pamela L Wolters, Staci Martin, Said Farschtschi, Ignacio Blanco, Zhongping Chen, Luiz Guilherme Darrigo, Marica Eoli, James R Whittle and 10 more

Abstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

38 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. SARC031: A Phase II Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  5. Review
  6. Article
  7. Review
  8. Article
  9. Management of plexiform neurofibromas in neurofibromatosis type 1: An Italian Delphi consensus.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  10. Review
  11. Bridging the gap: integrating hereditary cancer into precision oncology.European journal of human genetics : EJHG · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
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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

20 authors.

Alice P ChenDivision of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, Bethesda, MD, USA. Electronic address: chenali@mail.nih.gov.
Geraldine O'Sullivan CoyneDivision of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, Bethesda, MD, USA; Mater Misericordiae University Hospital, Dublin, Ireland.
Pamela L WoltersPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Staci MartinPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Said FarschtschiDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ignacio BlancoClinical Genetics Department, Hospital Germans Trias I Pujol, Barcelona, Spain.
Zhongping ChenDepartment of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China.
Luiz Guilherme DarrigoDepartment of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Marica EoliDepartment of Experimental Neuro-oncology, Fondazione IRCCS Besta, Milan, Italy.
James R WhittleDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia.
Yoshihiro NishidaDepartment of Rehabilitation, Nagoya University Hospital, Nagoya, Japan.
Rosa LamarcaAlexion AstraZeneca Rare Disease, Barcelona, Spain.
Randolph de la Rosa RodriguezAlexion AstraZeneca Rare Disease, MA, USA.
Ayo AdeyemiAlexion AstraZeneca Rare Disease, MA, USA.
Idoia HerreroAlexion AstraZeneca Rare Disease, Barcelona, Spain.
Nereida LlorenteAlexion AstraZeneca Rare Disease, Barcelona, Spain.
Scott J DiedeMerck, Rahway, NJ, USA.
Eva DombiPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pierre WolkensteinDepartment of Dermatology (CERENEF), Henri-Mondor Hospital, APHP, UPEC, Créteil, France; INSERM CIC 1430, Créteil, France.
KOMET study investigators

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

backgroundCurrently, no worldwide approved therapies exist for adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas. The KOMET study aimed to evaluate selumetinib (ARRY-142886, AZD6244) efficacy and safety in this population.

methodsThis ongoing multicentre, international, randomised, placebo-controlled, phase 3, parallel, double-blind trial randomly assigned adults with NF1-plexiform neurofibroma 1:1 to 28-day cycles of oral selumetinib 25 mg/m

findingsOverall, of 184 participants enrolled, 145 adults were randomly assigned to selumetinib (n=71) or placebo (n=74). Selumetinib led to a rapid response (median 3·7 months), with an objective response rate of 20% (n=14/71; 95% CI 11·2 to 30·9) by cycle 16 versus 5% (n=4/74; 1·5 to 13·3) with placebo (p=0·011). Participants with baseline chronic pain intensity scores of at least 3 had a greater reduction in score at cycle 12 with selumetinib versus placebo (least-squares mean [SE] -2·0 [0·30] -2·6 to -1·4, vs -1·3 [0·29] -1·8 to -0·7; p=0·070), although this did not reach significance; and a clinically meaningful improvement from baseline. Change from baseline to cycle 12 in PlexiQoL total scores between treatment groups was not significant (least-squares mean difference [SE] -0·1 [0·59]; -1·2 to 1·1). Adverse events were consistent with the known selumetinib safety profile.

interpretationIn the first international, randomised, placebo-controlled trial in adults with NF1-plexiform neurofibromas, selumetinib achieved a significant objective response rate versus placebo. No new safety concerns were identified. The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, reduction in analgesia, and decrease in pain interference over placebo show that selumetinib is effective at treating plexiform neurofibromas in adults with NF1.

fundingAstraZeneca as part of an alliance between AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck, Rahway, NJ, USA.

Indexed as

BenzimidazolesNeurofibroma, PlexiformNeurofibromatosis 1AdolescentAdultCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment OutcomeYoung AdultAZD 6244Benzimidazoles

Identifiers

PMID40473450
PMCPMC12285420

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.