Faculty Collaboration Database

Clinical trial design in the era of precision medicine. Genome Med 2022 Aug 31;14(1):101

Date

09/01/2022

Pubmed ID

36045401

Pubmed Central ID

PMC9428375

DOI

10.1186/s13073-022-01102-1

Scopus ID

2-s2.0-85137034260 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

Recent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant standard phase I, II, and III protocols, allowing for accelerated drug evaluation and approval and molecular-based individualized treatment. Furthermore, real-world data, as well as exploitation of digital apps and structured observational registries, and the utilization of machine learning and/or artificial intelligence, may further accelerate knowledge acquisition. Overall, clinical trials have evolved, shifting from tumor type-centered to gene-directed and histology-agnostic trials, with innovative adaptive designs and personalized combination treatment strategies tailored to individual biomarker profiles. Some, but not all, novel trials now demonstrate that matched therapy correlates with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To further improve the precision medicine paradigm, the strategy of matching drugs to patients based on molecular features should be implemented earlier in the disease course, and cancers should have comprehensive multi-omic (genomics, transcriptomics, proteomics, immunomic) tumor profiling. To overcome cancer complexity, moving from drug-centric to patient-centric individualized combination therapy is critical. This review focuses on the design, advantages, limitations, and challenges of a spectrum of clinical trial designs in the era of precision oncology.

Author List

Fountzilas E, Tsimberidou AM, Vo HH, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Artificial Intelligence
Clinical Trials as Topic
Humans
Neoplasms
Precision Medicine
Proteomics