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Poster display session

5154 - FGFR 360º RESISTANCE: establishing a translational research framework in FGFR-altered (FGFRalt) patients (pt) treated with fibroblast growth factor receptor inhibitors (FGFRinh).

Date

11 Sep 2017

Session

Poster display session

Presenters

Cinta Hierro

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

C. Hierro1, M. Sánchez-Guixé2, F. Ruiz-Pace3, J. Jimenez4, L. Maynes5, A. Azaro6, J. Martin-Liberal5, M. Ochoa de Olza5, I. Braña5, M. Vieito6, A. Villanueva7, H.G. Palmer8, J. Arribas9, P. Nuciforo10, A. Vivancos11, E. Garralda6, R. Dienstmann12, J. Tabernero1, V. Serra2, J. Rodon1

Author affiliations

  • 1 Medical Oncology, Vall d'Hebron University Hospital, 08015 - Barcelona/ES
  • 2 Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology, 08015 - Barcelona/ES
  • 3 Oncology Data Science Group (odyssey), Vall d'Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 4 Molecular Oncology Group, Vall d'Hebron Institute of Oncology, 08015 - Barcelona/ES
  • 5 Molecular Therapeutics Research Unit, Vall d'Hebron Institute of Oncology, 08015 - Barcelona/ES
  • 6 Molecular Therapeutics Research Unit, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 7 Catalan Institute Of Oncology (ico)-hospitalet, Research Drug Resistance Group and Xenografts, 08100 - Hospitalet de Llobregat/ES
  • 8 Stem Cells And Cancer Group, Vall d`Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 9 Growth Factors Group, Vall d`Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 10 Molecular Oncology Group, Vall d´Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 11 Cancer Genomics Group, Vall d´Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 12 Oncology Data Science (odyssey) Group, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
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Resources

Abstract 5154

Background

Pt selection is critical for the future development of FGFRinh. Our institution aimed to implement a translational platform to obtain samples of FGFRalt pt included in phase 1 trials.

Methods

Prospective generation of a collection of pt samples with molecularly-selected FGFRalt tumors [amplified(amp)/mRNA high expression(mRNAh)/mutated(mut)/translocated(trans)]. We developed a protocol to obtain serial biopsies (bx) during therapy with an FGFRinh, including warm autopsies, for patient-derived xenografts (PDXs) generation. We collected plasma for analysis of circulating tumor DNA (ctDNA). Clinical benefit (ClinBen) was defined as any tumor shrinkage or disease control for 4 months.

Results

From 2014 to 2017, 40 FGFRalt pt were included [FGFRamp (20)/mRNAh (7)/mut(17)/trans (3)]. 30 cases received an FGFRinh [multi-tyrosin kinase (7), selective reversible-(8) or irreversible-FGFR1-4inh (14) or FGFR4inh (1)]. 8 cases achieved ClinBen (5 breast - 2 FGFR1amp, 2 FGFR1mut, 1 11q+FGFR2amp-/1 biliary tract FGFR2trans/1 head&neck FGFR1mRNAh/1 mullerian carcinosarcoma FGFR2mut). PDXs/bx after progression to FGFRinh (10) and warm autopsies of responding pt (2) will serve to study tumor heterogeneity and resistance mechanisms using novel high-throughput technologies. All PDXs (16 growing/14 in observation) will help in identifying potential predictive biomarkers and further characterizing the mechanism of action of FGFRinh in vivo. In vitro functional profiling of oncogenic activity of FGFRmut (17) will be performed. Blood samples will serve for developing in-house cfDNA analysis to monitor genomic evolution of these 40 pt.

Conclusions

We have succesfully developed a powerful precision medicine framework for linking the molecular biology with the best tumor models in parallel with early clinical research. By integrating the knowledge obtained from the analysis of relevant samples, we aim to validate future hypothesis-driven therapies for selected FGFRalt pt and guide the successful development of FGFRinh. Co-funded by ISCIII-FEDER (PI15/00360).

Clinical trial identification

Legal entity responsible for the study

Vall d'Hebron Institute of Oncology

Funding

ISCIII-FEDER

Disclosure

C. Hierro: Research fundings from Bayer A. Vivancos: Member of advisory boards for AztraZeneca, Sysmex, Merck. J. Tabernero: Member of advisory boards for Amgen, Bayer, Boehringer, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Symphogen, Taiho and Takeda V. Serra: Research fundings from Bayer HealthCare J. Rodon: Member of advisory boards for Novartis, Lilly, Orion and has received research fundings from Principia and Bayer All other authors have declared no conflicts of interest.

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