The Role of Phase III Trials in Modern Drug Development

  • Janet E. Murphy
  • Lecia V. Sequist
  • Bruce A. Chabner
Part of the Cancer Drug Discovery and Development book series (CDD&D)


While the backbone of cancer treatment remains cytotoxic chemotherapy, modern cancer research has increased our understanding of the molecular pathogenesis of cancer and, in some cases, identified driver oncogenes. The small molecule imatinib, for example, which specifically targets the BCR-ABL and CKIT kinases, has revolutionized the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors.

In this chapter, we review the traditional path to drug development and FDA approval. We discuss the many disease settings in which the long road from phase I to phase III clinical trials remains relevant. We then explore two case studies: lung cancer and melanoma, in which identification of oncogene-addicted pathways allowed for phase I trial design with cohorts enriched with patients who harbored translocations/mutations in EML4-ALK and BRAF, respectively, with rapid appreciation of antitumor activity and an abbreviated path to drug approval. Here, the traditional phase III model is less relevant. We explore the ethics of drug development in the targeted therapy era and offer several solutions for accelerating drug evaluation where oncogene-directed therapy holds great promise in selected patients.


Targeted therapies Phase III trials Genotyping of tumors Ethical considerations in trial design 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Janet E. Murphy
    • 1
  • Lecia V. Sequist
    • 1
  • Bruce A. Chabner
    • 2
  1. 1.Harvard Medical School and Massachusetts General HospitalMailstopUSA
  2. 2.Department of MedicineHarvard Medical School, MGH Cancer Center, Massachusetts General HospitalBostonUSA

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