The idea of combining drugs and diagnostics in oncology is not new. When the selective estrogen receptor modulator tamoxifen was developed in the 1970’s for the treatment of breast cancer, data on estrogen receptor status was correlated with the treatment outcome. Based on a phase II study performed in patients with advanced breast cancer, published in 1976, the investigators concluded: “A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the diagnostic test as a means to select patients for tamoxifen treatment” (1). Despite the fact that this conclusion was drawn more than 35 years ago the adaptation of the drug-diagnostic co-development model has been relatively slow and it is only within the last decade that it has gained more widespread acceptance. The parallel development of the monoclonal antibody trastuzumab and the companion diagnostics assay for HER2 protein overexpression seems to have served as an inspiration to the pharma companies, and the number of drug-diagnostic co-development projects within oncology is now rapidly increasing.
Genomic sequencing has shown that marked heterogeneity exists in cancer and hence “standard” treatments will seldom work for everyone. The taxonomy of classifying the cancer diseases, according to its site of origin and histology, also seems to be far from optimal when it comes to the treatment decision. The philosophy of “one-disease-one-target-one drug” is history and the improvement in cancer pharmacotherapy must come from an increased understanding of the underlying molecular mechanisms in the individual patient. These mechanisms are of a complex nature and we are far from a complete understanding. However, what we do understand is that drugs work at the molecular level, and it is here we must seek the solution to a more rational drug development process and the subsequent treatment of the patients in the clinic (2).
In the drug-diagnostic co-development model the drug and the diagnostic are developed in parallel, and several study designs have been used or suggested in order to demonstrate clinical utility of the drug-diagnostic combinations. These designs are based on the traditional randomized study, which have certain limitations as they can only answer a single or few questions at a time. With the increased knowledge on both inter- and intratumor heterogeneity new study designs that can handle multiple variables need to be developed. Thus, the implementation of more pragmatic clinical trial designs has been suggested in order to speed up the translation research and to shorten the time between basic research and clinical development (3).
This Research Topic aims to cover different aspects related to drug-diagnostic co-development in oncology, such as drug development issues, clinical trial designs, and regulatory science. The topic will also seek to cover the development of companion diagnostics, including methodological issues such as biomarker selection, establishment of assay cut-off value, analytical validation and clinical utility. Articles on drug/biomarker research and clinical development are welcome as well as reviews, perspectives, and brief communications.
1. Lerner HJ, Band PR, Israel L, Leung BS. Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. Cancer Treat Rep 1976; 60: 1431-1435.
2. Jørgensen JT. A Changing Drug Development Process in the Era of Personalized Medicine. Drug Discov Today 2011; 16: 891-897.
3. Lesko LJ, Zineh I, Huang SM. What is clinical utility and why should we care? Clin Pharmacol Ther 2010; 88:729-733.
The idea of combining drugs and diagnostics in oncology is not new. When the selective estrogen receptor modulator tamoxifen was developed in the 1970’s for the treatment of breast cancer, data on estrogen receptor status was correlated with the treatment outcome. Based on a phase II study performed in patients with advanced breast cancer, published in 1976, the investigators concluded: “A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the diagnostic test as a means to select patients for tamoxifen treatment” (1). Despite the fact that this conclusion was drawn more than 35 years ago the adaptation of the drug-diagnostic co-development model has been relatively slow and it is only within the last decade that it has gained more widespread acceptance. The parallel development of the monoclonal antibody trastuzumab and the companion diagnostics assay for HER2 protein overexpression seems to have served as an inspiration to the pharma companies, and the number of drug-diagnostic co-development projects within oncology is now rapidly increasing.
Genomic sequencing has shown that marked heterogeneity exists in cancer and hence “standard” treatments will seldom work for everyone. The taxonomy of classifying the cancer diseases, according to its site of origin and histology, also seems to be far from optimal when it comes to the treatment decision. The philosophy of “one-disease-one-target-one drug” is history and the improvement in cancer pharmacotherapy must come from an increased understanding of the underlying molecular mechanisms in the individual patient. These mechanisms are of a complex nature and we are far from a complete understanding. However, what we do understand is that drugs work at the molecular level, and it is here we must seek the solution to a more rational drug development process and the subsequent treatment of the patients in the clinic (2).
In the drug-diagnostic co-development model the drug and the diagnostic are developed in parallel, and several study designs have been used or suggested in order to demonstrate clinical utility of the drug-diagnostic combinations. These designs are based on the traditional randomized study, which have certain limitations as they can only answer a single or few questions at a time. With the increased knowledge on both inter- and intratumor heterogeneity new study designs that can handle multiple variables need to be developed. Thus, the implementation of more pragmatic clinical trial designs has been suggested in order to speed up the translation research and to shorten the time between basic research and clinical development (3).
This Research Topic aims to cover different aspects related to drug-diagnostic co-development in oncology, such as drug development issues, clinical trial designs, and regulatory science. The topic will also seek to cover the development of companion diagnostics, including methodological issues such as biomarker selection, establishment of assay cut-off value, analytical validation and clinical utility. Articles on drug/biomarker research and clinical development are welcome as well as reviews, perspectives, and brief communications.
1. Lerner HJ, Band PR, Israel L, Leung BS. Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. Cancer Treat Rep 1976; 60: 1431-1435.
2. Jørgensen JT. A Changing Drug Development Process in the Era of Personalized Medicine. Drug Discov Today 2011; 16: 891-897.
3. Lesko LJ, Zineh I, Huang SM. What is clinical utility and why should we care? Clin Pharmacol Ther 2010; 88:729-733.
