TY - JOUR
T1 - Innovative trial design in precision oncology
AU - Tsimberidou, Apostolia M.
AU - Müller, Peter
AU - Ji, Yuan
N1 - Funding Information:
This work was supported in part by the National Institutes of Health/National Cancer Institute award number P30 CA016672 to The University of Texas MD Anderson Cancer Center, and in part by the National Institutes of Health/National Cancer Institute award number R01 CA132897 to Dr. Peter Müller and to Dr. Yuan Ji.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2022/9
Y1 - 2022/9
N2 - Genomic profiling technologies have enabled the development of targeted therapies designed to target specific biomarkers and molecular pathways involved in the pathophysiology of tumor initiation, metastasis, and drug resistance. In recent years, clinical trials with innovative design focus on the development of novel agents based on specific patient molecular alterations or other tumor characteristics and include patients with heterogenous tumor types. Precision oncology studies with innovative design associated with novel dose-finding approaches and data analysis focusing on subgroups of patients are characteristic of master protocols. Real-world data, patient-reported outcomes, and N-of-1 trials enhance the knowledge base of evidence to deliver personalized treatment to patients. Master protocols accelerate drug development by enabling simultaneous multiple sub-studies that match the patient's tumor molecular profile with experimental treatment arms. However, the increased flexibility of precision oncology trials is often associated with small subpopulations of patients, which may be underpowered to draw statistically robust conclusions. Despite their limitations, innovative clinical trials continue to rapidly translate the emerging discoveries of novel drugs into unprecedented clinical outcomes in patients with cancer and to accelerate the implementation of precision oncology.
AB - Genomic profiling technologies have enabled the development of targeted therapies designed to target specific biomarkers and molecular pathways involved in the pathophysiology of tumor initiation, metastasis, and drug resistance. In recent years, clinical trials with innovative design focus on the development of novel agents based on specific patient molecular alterations or other tumor characteristics and include patients with heterogenous tumor types. Precision oncology studies with innovative design associated with novel dose-finding approaches and data analysis focusing on subgroups of patients are characteristic of master protocols. Real-world data, patient-reported outcomes, and N-of-1 trials enhance the knowledge base of evidence to deliver personalized treatment to patients. Master protocols accelerate drug development by enabling simultaneous multiple sub-studies that match the patient's tumor molecular profile with experimental treatment arms. However, the increased flexibility of precision oncology trials is often associated with small subpopulations of patients, which may be underpowered to draw statistically robust conclusions. Despite their limitations, innovative clinical trials continue to rapidly translate the emerging discoveries of novel drugs into unprecedented clinical outcomes in patients with cancer and to accelerate the implementation of precision oncology.
KW - Basket trial
KW - Biomarkers
KW - Personalized medicine
KW - Real world data
KW - Umbrella trial
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U2 - 10.1016/j.semcancer.2020.09.006
DO - 10.1016/j.semcancer.2020.09.006
M3 - Review article
C2 - 33022355
AN - SCOPUS:85094559899
SN - 1044-579X
VL - 84
SP - 284
EP - 292
JO - Seminars in cancer biology
JF - Seminars in cancer biology
ER -