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Precision Medicine Clinical Trials: Successes and Disappointments, Challenges and Opportunities – Lessons Learnt

  • Mark Abramovitz
  • Casey Williams
  • Pradip K. De
  • Nandini Dey
  • Scooter Willis
  • Brandon Young
  • Eleni Andreopoulou
  • W. Fraser Symmans
  • Jason K. Sicklick
  • Richard L. Schilsky
  • Vladimir Lazar
  • Catherine Bresson
  • John Mendelsohn
  • Razelle Kurzrock
  • Brian Leyland-Jones
Chapter

Abstract

The precision medicine (PM) revolution is well underway, and next-generation sequencing (NGS) is helping take cancer treatment to new levels. Finding actionable targets in real time is now a reality, and data from several clinical trials based on identified molecular alterations can be assessed and can help address the question of whether personalized treatment based on genomics produces superior survival outcomes compared with unselected treatment. Targeted treatment-based clinical trials have shown benefit in molecular subgroups of patients. Of further interest, it appears that genomics and immunotherapy are coupled to each other, since the immune system recognizes neo-antigens produced by the mutanome. Hence, some of the most important markers predicting response to immunotherapy are genomic markers, PDL1 amplification (for PD-1/PD-L1 checkpoint inhibitors), and tumor mutational burden. However, a number of challenges remain to be addressed if the use of molecular profiling-guided therapy in PM-designed clinical trials is to become the standard on which cancer treatment is based. In this chapter, we explore what it will take for PM trials that use molecular profiling as part of the eligibility criteria to be successful and the remaining hurdles that need to be overcome.

Keywords

Precision medicine Next-generation sequencing Targeted treatment Molecular profiling Personalized medicine 

Notes

Acknowledgments

We would like to acknowledge the Avera Cancer Institute, Sioux Falls, SD, for providing support for our research.

Conflicts of Interest

The authors have no conflicts of interest to declare.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mark Abramovitz
    • 1
  • Casey Williams
    • 2
  • Pradip K. De
    • 3
  • Nandini Dey
    • 4
  • Scooter Willis
    • 2
  • Brandon Young
    • 2
  • Eleni Andreopoulou
    • 5
  • W. Fraser Symmans
    • 6
  • Jason K. Sicklick
    • 7
  • Richard L. Schilsky
    • 8
  • Vladimir Lazar
    • 9
  • Catherine Bresson
    • 9
  • John Mendelsohn
    • 10
  • Razelle Kurzrock
    • 11
  • Brian Leyland-Jones
    • 4
  1. 1.Avera Cancer InstituteSioux FallsUSA
  2. 2.Center for Precision OncologyAvera Cancer InstituteSioux FallsUSA
  3. 3.Department of Molecular and Experimental MedicineAvera Cancer InstituteSioux FallsUSA
  4. 4.Department of Molecular and Experimental MedicineCenter for Precision Oncology, Avera Cancer InstituteSioux FallsUSA
  5. 5.Department of Medicine, Division of Hematology & Medical OncologyWeill Cornell Medicine/New York Presbyterian HospitalNew YorkUSA
  6. 6.MD Anderson Cancer CenterHoustonUSA
  7. 7.Division of Surgical Oncology, General Surgery Residency, Biorepository and Tissue Technology Shared ResourceMoores Cancer Center, University of California San Diego (UCSD), School of MedicineSan DiegoUSA
  8. 8.American Society of Clinical OncologyAlexandriaUSA
  9. 9.Win ConsortiumVillejuifFrance
  10. 10.Khalifa Institute for Personalized Cancer TherapyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  11. 11.Moores Cancer Center, UC San Diego Moores Cancer CenterLa JollaUSA

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