Evidence map›Paper›PMID 28176175›Full record

Trial reportBreast cancer research and treatment2017

Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study.

M Higgins, G Curigliano, V Dieras, S Kuemmel, G Kunz, P A Fasching, M Campone, T Bachelot, P Krivorotko, S Chan and 7 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01220128 (Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–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.

NCT01220128 phase2terminatednot on this map

Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer

TypeinterventionalSponsorGlaxoSmithKlineRan2011 to 2014Enrolled66ConditionsNeoplasms, BreastArmsGSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Placebo, Aromatase inhibitor, 5-Fluorouracil, Carboplatin AUC
3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
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

17 authors.

M HigginsDepartment of Medical Oncology, Mater Misericordiae University Hospital, Eccles St., Dublin, 7, Ireland. mhiggins@mater.ie.ORCID 0000-0001-5018-3026
G CuriglianoDivision of Early Drug Development, Istituto Europeo di Oncologia, Milan, Italy.
V DierasClinical Investigational Unit, Institut Curie, Paris, France.
S KuemmelBreast UnitKliniken Essen-Mitte, Essen, Germany.
G KunzDepartment of Obstetrics & Gynecology, St.-Johannes-Hospital, Dortmund, Germany.
P A FaschingDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-EMN, Erlangen, Germany.
M CamponeService d'Oncologie Médicale, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
T BachelotDepartment of Medical Oncology, Centre Leon Berard, Lyon, France.
P KrivorotkoPetrov Research Institute of Oncology, St. Petersburg, Russian Federation.
S ChanDepartment of Clinical Oncology, Nottingham University Hospital NHS Trust (City campus), Nottingham, UK.
A FerroUnit of Medical Oncology, Santa Chiara Hospital, Trento, Italy.
L SchwartzbergDivision of Hematology/Oncology, University of Tennessee Health Science Center, The West Clinic, Medical Oncology, Memphis, USA.
M GilletGSK Vaccines, Rixensart, Belgium.
P M De Sousa AlvesGSK Vaccines, Rixensart, Belgium.
V WascotteGSK Vaccines, Rixensart, Belgium.
F F LehmannGSK Vaccines, Rixensart, Belgium.
P GossMGH Cancer Center, Massachusetts General Hospital, Boston, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThis Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients.

methodsPatients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination.

resultsSixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely.

conclusionsConcurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.

Indexed as

Cancer VaccinesAntibodiesAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCombined Modality TherapyFemaleHumansImmunotherapyNeoadjuvant TherapyNeoplasm StagingRecombinant ProteinsTreatment OutcomeWT1 ProteinsAntibodiesAntigens, NeoplasmCancer VaccinesRecombinant ProteinsWT1 ProteinsBreast cancerImmunogenicityImmunotherapyNeoadjuvant therapySafetyWT1 antigen

Identifiers

PMID28176175
PMCPMC5332485

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.