Evidence map›Paper›PMID 26324738›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2016

Clinical and Translational Results of a Phase II, Randomized Trial of an Anti-IGF-1R (Cixutumumab) in Women with Breast Cancer That Progressed on Endocrine Therapy.

William J Gradishar, Denise A Yardley, Rachel Layman, Joseph A Sparano, Ellen Chuang, Donald W Northfelt, Gary N Schwartz, Hagop Youssoufian, Shande Tang, Ruslan Novosiadly and 5 more

Open access · greenAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% 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.

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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. Neuro-Cancer Interactions Shape Glioma Intratumoral Heterogeneity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  11. Review
  12. Article
  13. Postmarketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.The Journal of clinical endocrinology and metabolism · 2024
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. IGF-1 Stimulates Glycolytic ATP Production in MCF-7L Cells.International journal of molecular sciences · 2023
    Article
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

15 authors at 1 institution in 1 country.

William J GradisharNorthwestern University Feinberg School of Medicine, Chicago, Illinois. w-gradishar@northwestern.edu.
Denise A YardleySarah Cannon Research Institute, Nashville, Tennessee. Tennessee Oncology, PLLC, Nashville, Tennessee.
Rachel LaymanOhio State University Comprehensive Cancer Center, Columbus, Ohio.
Joseph A SparanoMontefiore Medical Center, Bronx, New York.
Ellen ChuangWeill Cornell Medical College, New York, New York.
Donald W NorthfeltMayo Clinic Cancer Center, Scottsdale, Arizona.
Gary N SchwartzDartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Hagop YoussoufianProgenics Pharmaceuticals, Tarrytown, New York.
Shande TangEli Lilly and Company, Bridgewater, New Jersey.
Ruslan NovosiadlyEli Lilly and Company, New York, New York.
Amelie ForestEli Lilly and Company, New York, New York.
Tuan S NguyenEli Lilly and Company, Indianapolis, Indiana.
Jan CosaertEli Lilly and Company, Bridgewater, New Jersey.
Dmitri GrebennikEli Lilly and Company, Bridgewater, New Jersey.
Paul HaluskaMayo Clinic Cancer Center, Rochester, Minnesota.
Northwestern University · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Training Program in Biostatistics for Cancer ResearchT32CA096520 · NCI · RICE UNIVERSITY · PI KIMMEL, MAREK, YUAN, YING · 2003 to 2023
$4.5M
NCI NIH HHS P30 CA023108NCI NIH HHS T32 CA096520
6 · The paper itself

Abstract

purposeThis phase II trial evaluated the efficacy and safety of cixutumumab, a human anti-insulin-like growth factor receptor 1 (IGF-1R) monoclonal IgG1 antibody, and explored potential biomarkers in postmenopausal women with hormone receptor-positive breast cancer. EXPERIMENTAL

designPatients with hormone receptor-positive breast cancer that progressed on antiestrogen therapy received (2:1 randomization) cixutumumab 10 mg/kg and the same antiestrogen (arm A) or cixutumumab alone (arm B) every 2 weeks (q2w). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety. Correlative analyses of IGF-1R, total insulin receptor (IR), and IR isoforms A (IR-A) and B (IR-B) expression in tumor tissue were explored.

resultsNinety-three patients were randomized (arm A, n = 62; arm B, n = 31). Median PFS was 2.0 and 3.1 months for arm A and arm B, respectively. Secondary efficacy measures were similar between the arms. Overall, cixutumumab was well tolerated. IGF-1R expression was not associated with clinical outcomes. Regardless of the treatment, lower IR-A, IR-B, and total IR mRNA expression in tumor tissue was significantly associated with longer PFS [IR-A: HR, 2.62 (P = 0.0062); IR-B: HR, 2.21 (P = 0.0202); and total IR: HR, 2.18 (P = 0.0230)] and OS [IR-A: HR, 2.94 (P = 0.0156); IR-B: HR, 2.69 (P = 0.0245); and total IR: HR, 2.72 (P = 0.0231)].

conclusionsCixutumumab (10 mg/kg) with or without antiestrogen q2w had an acceptable safety profile, but no significant clinical efficacy. Patients with low total IR, IR-A, and IR-B mRNA expression levels had significantly longer PFS and OS, independent of the treatment. The prognostic or predictive value of IR as a biomarker for IGF-1R-targeted therapies requires further validation.

Indexed as

AdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEstrogen Receptor ModulatorsFemaleHumansMiddle AgedPostmenopausePrognosisReceptor, IGF Type 1RNA, MessengerAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiomarkers, TumorcixutumumabEstrogen Receptor ModulatorsReceptor, IGF Type 1RNA, Messenger

Identifiers

PMID26324738
PMCPMC5548297
OpenAlexW1206791772

What OpenQuestion 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 OpenQuestion graph.