Evidence map›Paper›PMID 27686971›Full record

Trial reportClinical lung cancer2017

Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations.

Natasha B Leighl, Naiyer A Rizvi, Lopes Gilberto de Lima, Wichit Arpornwirat, Charles M Rudin, Alberto A Chiappori, Myung-Ju Ahn, Laura Q M Chow, Lyudmila Bazhenova, Arunee Dechaphunkul and 9 more

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

Trial report in Clinical lung cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 5 pooled it
4.1field-weighted citation impact, top 6% 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

29 citing papers in PubMed, 5 syntheses or guidelines pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

19 authors at 13 institutions in 4 countries.

Natasha B LeighlCancer Clinical Research Unit, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Naiyer A RizviDepartment of Hematology and Oncology, Columbia University Medical Center, New York, NY.
Lopes Gilberto de LimaOncoclinicas Group, Hcor Onco, Sao Paulo, SP, Brazil; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD.
Wichit ArpornwiratNational Cancer Research, Bangkok, Thailand.
Charles M RudinMemorial Sloan Kettering Cancer Center, New York, NY.
Alberto A ChiapporiMoffitt Cancer Center, Tampa, FL.
Myung-Ju AhnDepartment of Hematology and Oncology, Sungkyunkwan University, Seoul, South Korea.
Laura Q M ChowUniversity of Washington, Seattle, WA.
Lyudmila BazhenovaDepartment of Clinical Oncology, School of Medicine, UC San Diego Moores Cancer Center, San Diego, CA.
Arunee DechaphunkulDepartments of Pathology, Hematology, and Surgery, Prince of Songkla University, Songkhla, Thailand.
Patrapim SunpaweravongDepartment of Internal Medicine, Prince of Songkla University, Songkhla, Thailand.
Keith EatonPrince of Songkla University, Songkhla, Thailand; Medical Oncology at University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, WA.
Jihong ChenAstellas, Northbrook, IL.
Sonja MedleyAstellas, Northbrook, IL.
Srinivasu PoondruAstellas, Northbrook, IL.
Margaret SinghAstellas, Northbrook, IL.
Joyce SteinbergAstellas, Northbrook, IL.
Rosalyn A JuergensJuravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, ON, Canada. Electronic address: juergensr@hhsc.ca.
Shirish M GadgeelKarmanos Cancer Institute, Wayne State University, Detroit, MI; Hematology-Oncology, Wayne State University, Detroit, MI.
Astellas Pharma (United States) · USPrince of Songkla University · THUniversity of Washington · USColumbia University Irving Medical Center · USJohns Hopkins Medicine · USJuravinski Cancer Centre · CAMemorial Sloan Kettering Cancer Center · USMoffitt Cancer Center · USMoores Cancer CenterNational Cancer Institute of Thailand · THPrincess Margaret Cancer Centre · CASungkyunkwan University · KRWayne State University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

introductionFirst-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes. PATIENTS AND

methodsWe performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non-small-cell lung cancer. Patients received linsitinib 150 mg twice daily or placebo plus erlotinib 150 mg once daily on continuous 21-day cycles. The primary end point was progression-free survival.

resultsAfter randomization of 88 patients (44 each arm), the trial was unblinded early owing to inferiority in the linsitinib arm. The median progression-free survival for the linsitinib versus the placebo group was 8.4 months versus 12.4 months (hazard ratio, 1.37; P = .29). Overall response rate (47.7% vs. 75.0%; P = .02) and disease control rate (77.3% vs. 95.5%; P = .03) were also inferior. Whereas most adverse events were ≤ grade 2, linsitinib plus erlotinib was associated with increased adverse events that led to decreased erlotinib exposure (median days, 228 vs. 305). No drug-drug interaction was suggested by pharmacokinetic and pharmacodynamic results.

conclusionAdding linsitinib to erlotinib resulted in inferior outcomes compared with erlotinib alone. Further understanding of the signaling pathways and a biomarker that can predict efficacy is needed prior to further clinical development of IGF-1R inhibitors in lung cancer.

Indexed as

AdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDouble-Blind MethodErbB ReceptorsErlotinib HydrochlorideFemaleFollow-Up StudiesHumansImidazolesLung Neoplasms3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanolBiomarkers, TumorEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideImidazolesPyrazinesCombinationEpidermal growth factor receptor inhibitorFirst-line therapyInsulin-like growth factor-1 inhibitorTyrosine kinase inhibitor

Identifiers

PMID27686971
PMCPMC5474312
OpenAlexW2513734563

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.