Evidence map›Paper›PMID 21519026›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2011

Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers.

Tanios Bekaii-Saab, Mitch A Phelps, Xiaobai Li, Motoyasu Saji, Laura Goff, John Sae Wook Kauh, Bert H O'Neil, Stephanie Balsom, Catherine Balint, Ryan Liersemann and 8 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00553332 (A Phase 2 Study of AZD6244 in Biliary Cancers), which is not on this map. Cited by 148 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 1 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.

NCT00553332 phase2completednot on this map

A Phase 2 Study of AZD6244 in Biliary Cancers

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2007 to 2013Enrolled29ConditionsLiver and Intrahepatic Biliary Tract Cancer, Recurrent Extrahepatic Bile Duct Cancer, Unresectable Extrahepatic Bile Duct CancerArmsselumetinib, laboratory biomarker analysis
3 · Its place in the literature

Who cites it

148 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  6. Trial
  7. Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Trial
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  13. Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014
    Trial
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  16. Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011
    Trial
  17. Article
  18. Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026
    Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Tanios Bekaii-SaabThe Ohio State University Comprehensive Cancer Center--James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA. Tanios.Bekaii-Saab@osumc.edu
Mitch A Phelps
Xiaobai Li
Motoyasu Saji
Laura Goff
John Sae Wook Kauh
Bert H O'Neil
Stephanie Balsom
Catherine Balint
Ryan Liersemann
Vasily V Vasko
Mark Bloomston
William Marsh
L Austin Doyle
Gilian Ellison
Michael Grever
Matthew D Ringel
Miguel A Villalona-Calero

Funding

University of Iowa Clinical and Translational Science Program (TL1)UL1RR025755 · NCRR · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2008 to 2011
$26.3M
NCI NIH HHS N01 CM062207NCI NIH HHS N01-CM62207NCRR NIH HHS UL1 RR025755
6 · The paper itself

Abstract

purposeBiliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC. PATIENTS AND

methodsThis was a multi-institutional phase II study of selumetinib at 100 mg given orally twice per day to patients with advanced BC. The primary end point was response rate. All patients were required to provide tissue before enrolling. The levels of phosphorylated ERK (pERK) and AKT (pAKT) were assessed by immunohistochemistry. Tumors were genotyped for the presence of BRAF- and/or RAS-activating mutations.

resultsTwenty-eight eligible patients with a median age of 55.6 years were enrolled. Thirty-nine percent of patients had received one prior systemic therapy. Three patients (12%) had a confirmed objective response. Another 17 patients (68%) experienced stable disease (SD), 14 of whom (56%) experienced prolonged SD (> 16 weeks). Patients gained an average nonfluid weight of 8.6 pounds. Median progression-free survival was 3.7 months (95% CI, 3.5 to 4.9) and median overall survival was 9.8 months (95% CI, 5.97 to not available). Toxicities were mild, with rash (90%) and xerostomia (54%) being most frequent. Only one patient experienced grade 4 toxicity (fatigue). All patients had tissue available for analysis. No BRAF V600E mutations were found. Two patients with short-lived SD had KRAS mutations. Absence of pERK staining was associated with lack of response.

conclusionSelumetinib displays interesting activity and acceptable tolerability in patients with metastatic BC. Our results warrant further evaluation of selumetinib in patients with metastatic BC.

Indexed as

AdultAgedBenzimidazolesBiliary Tract NeoplasmsExtracellular Signal-Regulated MAP KinasesFemaleHumansMaleMAP Kinase Kinase 1MAP Kinase Kinase 2Middle AgedMutationNeoplasm MetastasisPhosphorylationProto-Oncogene ProteinsProto-Oncogene Proteins B-rafAZD 6244BenzimidazolesBRAF protein, humanExtracellular Signal-Regulated MAP KinasesKRAS protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2Proto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID21519026
PMCPMC3107751

What OpenQuestion holds

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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.