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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4348 - Differential gene expression profiles in poor vs good responders to maintenance vinflunine in patients (p) with advanced urothelial carcinoma (aUC): Preliminary results of biomarker analyses from the MAJA trial (SOGUG 2011/02)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Jose Luis Ramirez

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

J.L. Ramirez1, A. Font Pous2, J. Garcia-Donas3, B. Perez Valderrama4, I. Aguirre Egaña5, L. Nonell6, V. Ruiz de Porras Fontdevila7, M. Mallo8, D. Balañá9, J.A. Virizuela10, U. Anido11, M..M. Llorente Ostiategui12, M.A. Gonzalez del Alba Baamonde13, N. Lainez14, B. Mellado15, M.A. Climent Duran16, J. Bellmunt17

Author affiliations

  • 1 Cancer Molecular Biology Laboratory, Catalan Institute of Oncology (ICO) - Germans Trias i Pujol Health Sciences Research Institute (IGTP), 08916 - Badalona/ES
  • 2 Medical Oncology, Institut Català d' Oncologia, 8916 - Badalona/ES
  • 3 Genitourinary, Ginecologycal, Skin And Rare Tumors Unit, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 4 Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 5 Programa De Medicina Predictivia I Personalitzada Del Càncer, Catalan Institute of Oncology (ICO) - Germans Trias i Pujol Health Sciences Research Institute (IGTP), Badalona/ES
  • 6 Microarrays Analysis Department, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona/ES
  • 7 Resistance, Chemotherapy And Predictive Biomarkers Department, Catalan Institute of Oncology (ICO) - Germans Trias i Pujol Health Sciences Research Institute (IGTP), Badalona/ES
  • 8 Josep Carreras Leukaemia Research Institute, Catalan Institute of Oncology (ICO) - Germans Trias i Pujol Health Sciences Research Institute (IGTP), Badalona/ES
  • 9 Cancer Molecular Biology Laboratory, Catalan Institute of Oncology (ICO) - Germans Trias i Pujol Health Sciences Research Institute (IGTP), Badalona/ES
  • 10 Medical Oncology, Hospital Virgen Macarena, 41009 - Sevilla/ES
  • 11 Medical Oncologist, CHU Santiago, Santiago/ES
  • 12 Oncología, Hospital General de Elda, 3600 - Elda/ES
  • 13 Medical Oncology, Hospital Universitario Son Espases, 7010 - Palma de Mallorca/ES
  • 14 Medical Oncology, Complejo Hospitalario de Navarra, Pamplona/ES
  • 15 Medical Oncology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 16 Medical Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 17 Medical Oncology, Hospital del Mar, 28023 - Barcelona/ES
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Resources

Abstract 4348

Background

Vinflunine is an antimicrotubule agent approved by the EMA for second-line treatment in p with aUC. However, no molecular biomarkers are currently available that can predict response to vinflunine in aUC. In the randomized phase II MAJA trial (NCT01529411) in p with aUC with disease control after a platinum-based regimen, maintenance vinflunine conferred a significant improvement in progression-free survival compared to best supportive care (Garcia-Donas et al. Lancet Oncol 2017). Pre-planned gene expression analyses aimed to identify biomarkers to predict response to maintenance vinflunine.

Methods

In the MAJA trial, 44 p received vinflunine. We have compared the gene expression profiles of eight poor responders to vinflunine (<4 cycles) and nine good responders (>12 cycles). RNA was isolated from FFPE tumor tissue collected during screening using the Covaris kit and gene expression levels were analyzed with Clariom S array (Thermo Fisher). Differential expression (DE), defined as p < 0.05 and |FC|>1.5, was determined with linear models for microarray data included in the limma and sva packages. Pre-ranked Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the DE genes.

Results

Hierarchical clustering of genes showed a DE between good and poor responders. DE were found in 31 genes, 13 of them were unregulated in good responders and 18 were unregulated in poor responders. In good responders, GSEA revealed overexpression of 72 genes related to G2M-checkpoint and of 61 genes related to E2F transcription factor. In poor responders, 73 genes related to epithelial-mesenchymal transition and 39 related to IL6/JAK/STAT3 were downregulated. We are currently validating these genes using qPCR to determine a gene expression profile associated with response to maintenance vinflunine.

Conclusions

Our preliminary results suggest that microarray analysis could identify a gene expression signature to predict response to maintenance vinflunine, which will be useful in selecting treatment for p with aUC. Complete results of the analyses will be reported.

Clinical trial identification

NCT01529411; EudraCT: 2011-001271-39.

Legal entity responsible for the study

Spanish Oncology Genitourinary Group.

Funding

Spanish Oncology Genitourinary Group.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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