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Prediction of response to everolimus in neuroendocrine tumors: evaluation of clinical, biological and histological factors

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Summary

Objectives Several targeted therapies are available for metastatic neuroendocrine tumours (NETs) but no predictive factor of response to these treatments has been identified yet. Our aim was to identify and evaluate clinical, biological, histological and functional markers of response to everolimus. Methods We retrospectively reviewed 53 patients with NETs treated with everolimus (68 % in clinical trials). Clinical, biological and histological data were analyzed. The functional marker p-p70S6K, a main effector of the mTOR pathway, was studied by immunohistochemistry in 43 cases. Prognostic factors of progression-free survival (PFS) were studied by Kaplan Meier analysis. Results All patients had metastatic and progressive disease before everolimus treatment. Objective response was 9 % and median PFS was 8.1 (4.7–11.5) months. Hypercholesterolemia (HR = 0.13, p < 0.0001) was associated with longer PFS, whereas presence of bone metastases (HR = 3.1, p < 0.001) and overexpression of p-p70S6K by tumor cells (HR = 2.5, p = 0.01) were associated with shorter PFS under everolimus at multivariate analysis. Conclusion Clinical markers are not useful to predict response to everolimus. However, occurrence of hypercholesterolemia under treatment may be an early marker of response. Prospective studies are required to confirm these results and to assess whether p-p70S6K immunostaining is a prognostic or predictive marker of no-response to everolimus.

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Author contributions

Study design: NB, CV, CR, JYS, TW

Collection of data: NB, VH, JYS, JB, PM, TW

Writing the manuscript: NB, JYS, TW

Approval of the manuscript: all authors

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Authors and Affiliations

  1. Service d’hépatogastroentérologie et d’oncologie digestive, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon cedex 03, France

    Noura Benslama, Catherine Lombard-Bohas & Thomas Walter

  2. INSERM, UMR 1052, Lyon Cancer Research Center, Faculté Laennec, 69372, Lyon cedex 08, France

    Noura Benslama, Julien Bollard, Cécile Vercherat, Patrick Massoma, Colette Roche, Valérie Hervieu, Jean-Yves Scoazec & Thomas Walter

  3. Université de Lyon, Université Claude Bernard Lyon 1, 69622, Villeurbanne cedex, France

    Noura Benslama, Valérie Hervieu & Thomas Walter

  4. Service Central d’Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon cedex 03, France

    Valérie Hervieu

  5. Medical Oncology Department, Centre Hospitalier Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon, Pierre-Bénite, France

    Julien Peron

Authors
  1. Noura Benslama
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  2. Julien Bollard
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  3. Cécile Vercherat
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  4. Patrick Massoma
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  5. Colette Roche
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  6. Valérie Hervieu
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  7. Julien Peron
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  8. Catherine Lombard-Bohas
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  9. Jean-Yves Scoazec
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  10. Thomas Walter
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Corresponding author

Correspondence to Thomas Walter.

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Conflict of interest

T Walter, JY Scoazec have acted as advisory board member for Ipsen, Pfizer and Novartis.

All other authors: no conflict of interest.

Funding

This study received financial support from Novartis and la Ligue Contre le Cancer du Rhône, France.

C Vercherat is recipient of a post-doctoral grant from LYric grant INCa-DGOS 4664.

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Benslama, N., Bollard, J., Vercherat, C. et al. Prediction of response to everolimus in neuroendocrine tumors: evaluation of clinical, biological and histological factors. Invest New Drugs 34, 654–662 (2016). https://doi.org/10.1007/s10637-016-0363-6

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  • DOI: https://doi.org/10.1007/s10637-016-0363-6

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