Evidence map›Paper›PMID 27460442›Full record

Trial reportThe Lancet. Oncology2016

Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial.

Marcia S Brose, Maria E Cabanillas, Ezra E W Cohen, Lori J Wirth, Todd Riehl, Huibin Yue, Steven I Sherman, Eric J Sherman

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01286753 (An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer), which is not on this map. Cited by 211 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
211citing papers in PubMed, 7 pooled it
28.5field-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.

NCT01286753 phase2completednot on this map

An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine

TypeinterventionalSponsorHoffmann-La RocheRan2011 to 2015Enrolled51ConditionsNeoplasmsArmsVemurafenib
3 · Its place in the literature

Who cites it

211 citing papers in PubMed, 7 syntheses or guidelines pooled it, 381 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Guideline
  5. Guideline
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Dabrafenib Versus Dabrafenib + Trametinib inThyroid : official journal of the American Thyroid Association · 2022
    Trial
  11. BRAF Inhibition inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018
    Trial
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
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  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Marcia S BroseDepartment of Otorhinolaryngology: Head and Neck Surgery, and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: brosem@mail.med.upenn.edu.
Maria E CabanillasDepartment of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ezra E W CohenMoores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Lori J WirthDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Todd RiehlProduct Development Clinical Oncology, Genentech Inc, South San Francisco, CA, USA.
Huibin YueBiostatistics, Genentech Inc, South San Francisco, CA, USA.
Steven I ShermanDepartment of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eric J ShermanDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The University of Texas MD Anderson Cancer Center · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USUniversity of California, San Diego · USUniversity of Pennsylvania · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
SPORE in Thyroid CancerP50CA172012 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI FAGIN, JAMES A · 2014 to 2018
$10.3M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA172012
6 · The paper itself

Abstract

backgroundAbout half of patients with papillary thyroid cancer have tumours with activating BRAF(V600E) mutations. Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial. We aimed to establish the activity of vemurafenib in patients with BRAF(V600E)-positive papillary thyroid cancer.

methodsWe did an open-label, non-randomised, phase 2 trial at ten academic centres and hospitals worldwide in patients aged 18 years or older with histologically confirmed recurrent or metastatic papillary thyroid cancer refractory to radioactive iodine and positive for the BRAF(V600E) mutation. Participants either had never received a multikinase inhibitor targeting VEGFR (cohort 1) or had been treated previously with a VEGFR multikinase inhibitor (cohort 2). Patients received vemurafenib 960 mg orally twice daily. The primary endpoint was investigator-assessed best overall response in cohort 1 (confirmed on two assessments 4 weeks or longer apart). Analyses were planned to have a minimum median follow-up of 15 months (data cutoff April 18, 2014) and were done in safety, intention-to-treat, and per-protocol populations. This trial is closed and is registered at ClinicalTrials.gov, number NCT01286753.

findingsBetween June 23, 2011, and Jan 15, 2013, 51 patients were enrolled to the study, 26 in cohort 1 and 25 in cohort 2. Median duration of follow-up was 18·8 months (IQR 14·2-26·0) in cohort 1 and 12·0 months (6·7-20·3) in cohort 2. Partial responses were recorded in ten of 26 patients in cohort 1 (best overall response 38·5%, 95% CI 20·2-59·4). Grade 3 or 4 adverse events were recorded in 17 (65%) of 26 patients in cohort 1 and 17 (68%) of 25 patients in cohort 2; the most common grade 3 and 4 adverse events were squamous cell carcinoma of the skin (seven [27%] in cohort 1, five [20%] in cohort 2), lymphopenia (two [8%] in each cohort), and increased γ-glutamyltransferase (one [4%] in cohort 1, three [12%] in cohort 2). Two individuals in cohort 2 died due to adverse events, one from dyspnoea and one from multiorgan failure, but neither was treatment related. Serious adverse events were reported for 16 (62%) of 26 patients in cohort 1 and 17 (68%) of 25 patients in cohort 2.

interpretationVemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. As such, this agent represents a potential new treatment option for these patients.

fundingF Hoffmann-La Roche.

Indexed as

Salvage TherapyAgedAntineoplastic AgentsBiomarkers, TumorCarcinoma, PapillaryFemaleFollow-Up StudiesHumansImmunoenzyme TechniquesIndolesIodine RadioisotopesLymphatic MetastasisMaleMiddle AgedMutationNeoplasm StagingAntineoplastic AgentsBiomarkers, TumorBRAF protein, humanIndolesIodine RadioisotopesProto-Oncogene Proteins B-rafSulfonamidesVemurafenib

Identifiers

PMID27460442
PMCPMC5532535
OpenAlexW2503674037

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.