Evidence map›Paper›PMID 29045520›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2017

Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

M Schlumberger, R Elisei, S Müller, P Schöffski, M Brose, M Shah, L Licitra, J Krajewska, M C Kreissl, B Niederle and 9 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00704730 (An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer), which is not on this map. Cited by 107 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 3 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.

NCT00704730 phase3completednot on this map

An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer

TypeinterventionalSponsorExelixisRan2008 to 2020Enrolled330ConditionsThyroid CancerArmsXL184, Placebo
3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  17. Selpercatinib in the treatment of thyroid cancer.Future oncology (London, England) · 2025
    Review
  18. The utility ofThyroid research · 2025
    Article
  19. Article
  20. Review

47 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

19 authors.

M SchlumbergerDepartment of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France. Electronic address: martin.schlumberger@gustaveroussy.fr.
R EliseiEndocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
S MüllerDepartment of Nuclear Medicine, University Hospital Essen, Essen, Germany.
P SchöffskiDepartment of General Medical Oncology, KU Leuven, Leuven; Laboratory of Experimental Oncology at the University Hospitals Leuven, KU Leuven, Leuven, Belgium.
M BroseDepartment of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia.
M ShahDepartment of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, USA.
L LicitraIRCCS Foundation, National Cancer Institute, Milan; University of Milan, Milan, Italy.
J KrajewskaMaria Skłodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Gliwice, Poland.
M C KreisslDepartment of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
B NiederleDivision of Surgical Endocrinology, Medical University of Vienna, Vienna, Austria.
E E W CohenUniversity of California San Diego Moores Cancer Center, La Jolla.
L WirthDepartment of Hematology/Oncology, Massachusetts General Hospital, Boston.
H AliHenry Ford Health System, Detroit.
D O ClaryExelixis, Inc, South San Francisco.
Y YaronExelixis, Inc, South San Francisco.
M MangeshkarExelixis, Inc, South San Francisco.
D BallDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore.
B NelkinDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore.
S ShermanDepartment of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrimary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. PATIENTS AND

methodsEXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported.

resultsMinimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis.

conclusionThe secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. TRIAL REGISTRATION NUMBER: NCT00704730.

Indexed as

Diagnostic ImagingAgedAnilidesCarcinoma, MedullaryDouble-Blind MethodFemaleFollow-Up StudiesHumansInternational AgenciesMalePrognosisPyridinesSurvival RateThyroid NeoplasmsAnilidescabozantinibPyridinescabozantinibmedullary thyroid canceroverall survivalprogression-free survivalRET M918T

Identifiers

PMID29045520
PMCPMC5834040

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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.