Evidence map›Paper›PMID 23248257›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2013

Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor.

Kevin B Kim, Richard Kefford, Anna C Pavlick, Jeffrey R Infante, Antoni Ribas, Jeffrey A Sosman, Leslie A Fecher, Michael Millward, Grant A McArthur, Patrick Hwu and 10 more

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013. 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 243 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 1 pooled it
24.6field-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.

NCT01037127 phase2completednot on this map

An Open-Label, Multi-Center Study to Investigate the Objective Response Rate, Safety, and Pharmacokinetics of GSK1120212, a MEK Inhibitor, in BRAF Mutation-positive Melanoma Subjects Previously Treated With or Without a BRAF Inhibitor

TypeinterventionalSponsorGlaxoSmithKlineRan2009 to 2013Enrolled97ConditionsCancerArmsGSK1120212
NCT03825289 phase1terminatednot on this mapstarted 2019, after this paper: background citation

THREAD: A Phase I Trial of Trametinib and Hydroxychloroquine in Patients With Advanced Pancreatic Cancer

TypeinterventionalSponsorUniversity of UtahRan2019 to 2025Enrolled25ConditionsMetastatic Pancreatic Carcinoma, Stage II Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic CancerArmsHydroxychloroquine, Trametinib
3 · Its place in the literature

Who cites it

243 citing papers in PubMed, 1 synthesis or guideline pooled it, 473 citations in OpenAlex.

  1. Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022
    Pooled it
  2. Trial
  3. Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131).Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  4. Trial
  5. Trial
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

183 more citing papers are in PubMed but not listed here.

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 at 1 institution in 1 country.

Kevin B KimDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. kkim@mdanderson.org
Richard Kefford
Anna C Pavlick
Jeffrey R Infante
Antoni Ribas
Jeffrey A Sosman
Leslie A Fecher
Michael Millward
Grant A McArthur
Patrick Hwu
Rene Gonzalez
Patrick A Ott
Georgina V Long
Olivia S Gardner
Daniele Ouellet
Yanmei Xu
Douglas J DeMarini
Ngocdiep T Le
Kiran Patel
Karl D Lewis
GlaxoSmithKline (Netherlands) · NL

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Clinical Investigation in Tumor ImmunotherapyK24CA097588 · NCI · VANDERBILT UNIVERSITY · PI SOSMAN, JEFFREY A · 2002 to 2012
$1.5M
NCI NIH HHS K24 CA097588
6 · The paper itself

Abstract

purposeBRAF mutations promote melanoma cell proliferation and survival primarily through activation of MEK. The purpose of this study was to determine the response rate (RR) for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients with metastatic BRAF-mutant melanoma. PATIENTS AND

methodsThis was an open-label, two-stage, phase II study with two cohorts. Patients with metastatic BRAF-mutant melanoma previously treated with a BRAF inhibitor (cohort A) or treated with chemotherapy and/or immunotherapy (BRAF-inhibitor naive; cohort B) were enrolled. Patients received 2 mg of trametinib orally once daily.

resultsIn cohort A (n = 40), there were no confirmed objective responses and 11 patients (28%) with stable disease (SD); the median progression-free survival (PFS) was 1.8 months. In cohort B (n = 57), there was one (2%) complete response, 13 (23%) partial responses (PRs), and 29 patients (51%) with SD (confirmed RR, 25%); the median PFS was 4.0 months. One patient each with BRAF K601E and BRAF V600R had prolonged PR. The most frequent treatment-related adverse events for all patients were skin-related toxicity, nausea, peripheral edema, diarrhea, pruritis, and fatigue. No cutaneous squamous cell carcinoma was observed.

conclusionTrametinib was well tolerated. Significant clinical activity was observed in BRAF-inhibitor-naive patients previously treated with chemotherapy and/or immunotherapy. Minimal clinical activity was observed as sequential therapy in patients previously treated with a BRAF inhibitor. Together, these data suggest that BRAF-inhibitor resistance mechanisms likely confer resistance to MEK-inhibitor monotherapy. These data support further evaluation of trametinib in BRAF-inhibitor-naive BRAF-mutant melanoma, including rarer forms of BRAF-mutant melanoma.

Indexed as

MutationAdultAgedAntineoplastic AgentsDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMaleMAP Kinase Kinase 1MAP Kinase Kinase 2MelanomaMiddle AgedNeoplasm StagingProto-Oncogene Proteins B-rafPyridonesAntineoplastic AgentsBRAF protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2Proto-Oncogene Proteins B-rafPyridonesPyrimidinonestrametinib

Identifiers

PMID23248257
PMCPMC4878037
OpenAlexW2144096834

What OpenQuestion holds

Textmetadata
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.