Evidence map›Paper›PMID 29122619›Full record

Trial reportEBioMedicine2017

Aurora A Functional Single Nucleotide Polymorphism (SNP) Correlates With Clinical Outcome in Patients With Advanced Solid Tumors Treated With Alisertib, an Investigational Aurora A Kinase Inhibitor.

Huifeng Niu, Hyunjin Shin, Feng Gao, Jacob Zhang, Brittany Bahamon, Hadi Danaee, Bohuslav Melichar, Russell J Schilder, Robert L Coleman, Gerald Falchook and 9 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 24% 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.

NCT01045421 phase1 / phase2completednot on this map

A Phase 1 Dose Escalation Study of MLN8237, an Aurora A Kinase Inhibitor, in Adult Patients With Nonhematological Malignancies, Followed by a Phase 2 of MLN8237 in Lung, Breast, Head and Neck, or Gastroesophageal Malignancies

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2010 to 2014Enrolled273ConditionsAdvanced Nonhematological Malignancies, Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Metastatic Breast CancerArmsMLN8237 (Alisertib)
NCT01091428 phase2completednot on this map

Randomized Phase 2 Study of MLN8237, an Aurora A Kinase Inhibitor, Plus Weekly Paclitaxel or Weekly Paclitaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Preceded by a Phase 1 Portion in Patients With Ovarian or Breast Cancer

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2010 to 2017Enrolled191ConditionsOvarian Carcinoma, Fallopian Tube Cancer, Peritoneal Cancer, Breast CarcinomaArmsAlisertib, Paclitaxel
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020
    Review
  12. Article
  13. Article
  14. Journal of oncology · 2019
    Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 10 institutions in 4 countries.

Huifeng NiuMillennium Pharmaceuticals, Inc., Cambridge, MA, USA. Electronic address: huifeng.niu@takeda.com.
Hyunjin ShinMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Feng GaoMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Jacob ZhangMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Brittany BahamonMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Hadi DanaeeMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Bohuslav MelicharDepartment of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
Russell J SchilderDepartment of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
Robert L ColemanThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gerald FalchookSarah Cannon Research Institute at HealthONE, Denver, CO, USA.
Antoine AdenisCentre Oscar Lambret, Lille, France.
Kian BehbakhtDepartment of Gynecologic Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
Angela DeMicheleAbramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth Claire DeesUNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
Kimberly PerezDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ursula MatulonisGynecologic Oncology Program, Dana-Farber Cancer Institute, Boston, MA, USA.
Piotr SawryckiDepartment of Oncology and Chemotherapy, L. Rydygiera District Hospital, Torun, Poland.
Dirk HuebnerMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Jeffrey EcsedyMillennium Pharmaceuticals, Inc., Cambridge, MA, USA.
Millennium Engineering and Integration (United States) · USDana-Farber Cancer Institute · USAbramson Cancer CenterCentre Oscar Lambret · FRPalacký University Olomouc · CZSarah Cannon · USThe University of Texas MD Anderson Cancer Center · USThomas Jefferson University · USUNC Lineberger Comprehensive Cancer CenterUniversity of Colorado Denver · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. Aurora A contains two functional single nucleotide polymorphisms (SNPs; codon 31 [F/I] and codon 57 [V/I]) that lead to functional changes. This study investigated the prognostic and predictive significance of these SNPs.

methodsThis study evaluated associations between Aurora A SNPs and overall survival (OS) in The Cancer Genome Atlas (TCGA) database. The Aurora A SNPs were also evaluated as predictive biomarkers for clinical outcomes to alisertib in two phase 2 studies (NCT01045421 and NCT01091428). Aurora A SNP genotyping was obtained from 85 patients with advanced solid tumors receiving single-agent alisertib and 122 patients with advanced recurrent ovarian cancer treated with alisertib plus weekly paclitaxel (n=62) or paclitaxel alone (n=60). Whole blood was collected prior to treatment and genotypes were analyzed by PCR.

findingsTCGA data suggested prognostic significance for codon 57 SNP; solid tumor patients with VV and VI alleles had significantly reduced OS versus those with II alleles (HR 1.9 [VI] and 1.8 [VV]; p<0.0001). In NCT01045421, patients carrying the VV alleles at codon 57 (n=53, 62%) had significantly longer progression-free survival (PFS) than patients carrying IV or II alleles (n=32, 38%; HR 0.5; p=0.0195). In NCT01091428, patients with the VV alleles at codon 57 who received alisertib plus paclitaxel (n=47, 39%) had a trend towards improved PFS (7.5months) vs paclitaxel alone (n=32, 26%; 3.8months; HR 0.618; p=0.0593). In the paclitaxel alone arm, patients with the VV alleles had reduced PFS vs modified intent-to-treat (mITT) patients (3.8 vs 5.1months), consistent with the TCGA study identifying the VV alleles as a poor prognostic biomarker. No significant associations were identified for codon 31 SNP from the same data set.

interpretationThese findings suggest that Aurora A SNP at codon 57 may predict disease outcome and response to alisertib in patients with solid tumors. Further investigation is warranted.

Indexed as

AdultAgedAllelesAurora Kinase AAzepinesBiomarkers, TumorDisease-Free SurvivalFemaleHumansMaleMiddle AgedNeoplasmsNeoplasm StagingPaclitaxelPolymorphism, Single NucleotideProtein Kinase InhibitorsAURKA protein, humanAurora Kinase AAzepinesBiomarkers, TumorMLN 8237PaclitaxelProtein Kinase InhibitorsPyrimidinesAlisertibAurora A kinase inhibitorCorrelative analysisPredictive biomarkerPrognosisSNP

Identifiers

PMID29122619
PMCPMC5704062
OpenAlexW2767004851

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.