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Designs and challenges for personalized medicine studies in oncology: focus on the SHIVA trial

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Abstract

Personalized medicine is defined by the National Cancer Institute as “a form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease.” In oncology, the term “personalized medicine” arose with the emergence of molecularly targeted agents. The prescription of approved molecularly targeted agents to cancer patients currently relies on the primary tumor location and histological subtype. Predictive biomarkers of efficacy of these modern agents have been exclusively validated in specific tumor types. A major concern today is to determine whether the prescription of molecularly targeted therapies based on tumor molecular abnormalities, independently of primary tumor location and histology, would improve the outcome of cancer patients. This new paradigm requires prospective validation before being implemented in clinical practice. In this paper, we will first review different designs, including observational cohorts, as well as nonrandomized and randomized clinical trials, that have been recently proposed to evaluate the relevance of this approach, and further discuss their advantages and drawbacks. The design of the SHIVA trial, a randomized proof-of-concept phase II trial comparing therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer will be detailed. Finally, we will discuss the multiple challenges associated with the implementation of personalized medicine in oncology, as well as perspectives for the future.

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Acknowledgments

This work is supported by the grant ANR-10-EQPX-03 from the Agence Nationale de le Recherche (Investissements d’avenir) and SiRIC (Site de Recherche Intégré contre le Cancer).

We would like to greatly thank Bernard Asselain (Institut Curie, Paris, France), Camille Barette (Institut Curie, Paris, France), Emmanuel Barillot (Institut Curie, Paris, France), Virginie Bernard (Institut Curie, Paris, France), Ivan Bièche (Institut Curie, Saint-Cloud, France), Jean-Yves Blay (Centre Léon Bérard, Lyon, France), Fanny Coffin (Institut Curie, Paris, France), David Cox (Centre Léon Bérard, Lyon, France), Olivier Delattre (Institut Curie, Paris France), Véronique Diéras (Institut Curie, Paris, France), Laurence Escalup (Institut Curie, Paris, France), Pierre Fumoleau (Centre Georges-François Leclerc, Dijon, France), Pierre Gestraud (Institut Curie, Paris, France), Alexandre Hamburger (Institut Curie, Paris, France), Elisabeth Hess (Institut Curie, Paris, France), Philippe Huppé (Institut Curie, Paris, France), Claude Huriet (Institut Curie, Paris, France), Philippe La Rosa (Institut Curie, Paris, France), Séverine Lair (Institut Curie, Paris, France), Alban Lermine (Institut Curie, Paris, France), Georges Lucotte (Institut Curie, Paris, France), Odette Mariani (Institut Curie, Paris, France), Didier Meseure (Institut Curie, Saint-Cloud, France), Emmanuel Mitry (Institut Curie, Saint-Cloud, France), Fabrice Mulot (Institut Curie, Paris, France), Lionel Perrier (Institut Paoli-Calmettes, Marseille, France), Corine Plancher (Institut Curie, Paris, France), François Prud’homme (Institut Curie, Paris, France), Sergio Roman-Roman (Institut Curie, Paris, France), Damien Salauze (Institut Curie, Paris, France), Xavier Sastre (Institut Curie, Paris, France), Lillian L. Siu (Princess Margaret Hospital, Toronto, Canada), Patricia Tresca (Institut Curie, Paris, France), Patrice Viens (Institut Paoli-Calmettes, Marseille, France), Ian Tannock (Princess Margaret Hospital, Toronto, Canada), Pierre Teillac (Institut Curie, Paris, France), Bruno Zeitouni (Institut Curie, Paris, France) for their fruitful advices.

Conflict of interest

None of the authors received funds or benefits directly related to this article.

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Authors and Affiliations

  1. Institut Curie, Paris, France

    Christophe Le Tourneau, Maud Kamal, David Gentien, Anne Vincent-Salomon, Anne-Lise Pouliquen, Nicolas Servant, Marc-Henri Stern, Sébastien Armanet, Thomas Rio Frio & Xavier Paoletti

  2. Centre Léon Bérard, Lyon, France

    Olivier Trédan

  3. Institut Claudius Régaud, Toulouse, France

    Jean-Pierre Delord

  4. Centre René Gauducheau, Nantes, France

    Mario Campone

  5. Institut Paoli-Calmettes, Marseille, France

    Anthony Goncalves

  6. Centre Georges-François Leclerc, Dijon, France

    Nicolas Isambert

  7. Université de Lorraine, EA 4360 and Centre Alexis Vautrin, Nancy, France

    Thierry Conroy

  8. INSERM UMR931, Marseille, France

    Anne-Gaëlle Le Corroller

  9. Unité INSERM/Institut Curie U900, Paris, France

    Christophe Le Tourneau & Xavier Paoletti

  10. Department of Medical Oncology, Clinical Trial Unit, Institut Curie, 26, rue d’Ulm, 75248, Paris Cedex 05, France

    Christophe Le Tourneau

Authors
  1. Christophe Le Tourneau
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  2. Maud Kamal
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  3. Olivier Trédan
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  4. Jean-Pierre Delord
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  5. Mario Campone
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  6. Anthony Goncalves
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  7. Nicolas Isambert
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  8. Thierry Conroy
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  9. David Gentien
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  10. Anne Vincent-Salomon
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  11. Anne-Lise Pouliquen
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  12. Nicolas Servant
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  13. Marc-Henri Stern
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  14. Anne-Gaëlle Le Corroller
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  15. Sébastien Armanet
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  16. Thomas Rio Frio
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  17. Xavier Paoletti
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Corresponding author

Correspondence to Christophe Le Tourneau.

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Le Tourneau, C., Kamal, M., Trédan, O. et al. Designs and challenges for personalized medicine studies in oncology: focus on the SHIVA trial. Targ Oncol 7, 253–265 (2012). https://doi.org/10.1007/s11523-012-0237-6

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  • DOI: https://doi.org/10.1007/s11523-012-0237-6

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