Therapeutics
Recent Advances and Future Challenges Using Biomarkers in Oncology Precision Medicine Introduction Current and future cancer treatment is expected to be shaped and guided by the use of biomarkers that will guide researchers and physicians at every stage of development from the basic understanding of cell transformation, to early cancer detection, to precision drug development, to long-term disease management. Historically, cancer treatment was empirical, driven mainly by the histology of the tumour and organs of origin, and how the average patient population responded to a treatment. Appreciation of pharmacologically tractable genetic lesions present in subpopulations of cancer patients was starting to be realised about 30 years ago. Demonstration of more and more exciting examples of lesion-specific targeted drugs effective in lesion–specific subpopulation of patients is becoming the norm in cancer therapy, as well as other therapeutic areas. The biopharmaceutical industry has also evolved their business model that historically assumed it should only develop drugs for “all comers,” even if they only worked for in a subset of patients. It was eventually realised that superior clinical outcomes justifies premium pricing, albeit restricted to a smaller sub-set of patients. In addition, it was quickly appreciated that many histologically different tumour types may also contain similar lesion-specific subpopulations that will expand the market size. Most importantly, significant benefits were also gained by collaterally avoiding treating patients that would likely only receive very marginal benefits, if any. This has decreased the size, time and cost of clinical trials yielding superior clinical results by avoiding treating patients that will have marginal benefits. This is the concept of Precision Medicine: choosing the right drug for the right patient at the right
dose. The foundation to enable this treatment strategy is having the companion diagnostic measuring a biomarker to identify/select the lesion-specific subpopulation of patients. The regulatory and 3rd party payer environments also evolved where companion diagnostics measuring specific biomarkers are fully integrated into the “label” of the drug, and reimbursement system appreciated the value of a companion biomarker to ensure the drug is being used selectively in the correct subpopulation of patients. This was coupled to the acceptance that premium was justified based upon superior clinical outcomes. Biomarkers and Precision Medicine Precision Medicine is now a routine therapeutic strategy where each cancer patient is screened for biomarkers to create a “cancer signature” that provides information to create a personalised treatment plan. Two figures below illustrate the shift in cancer care to a Precision Medicine approach using biomarkers: •
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In 2005, personalised medicines associated with biomarkers in their respective labels, represented only five percent of the new molecular entities approved by the FDA. In 2019, the figure was 42 percent In 2000, only 15 percent of all oncology clinical trials involved the use of biomarkers. In 2018, this figure was 55 percent.
Figure #1 illustrated the broad applications that biomarkers have in oncology. 1.
Biomarkers have proved to be critically important as screening tools for the detection and diagnosis of cancer (i.e. screening for PSA levels to help detect prostate cancer) 2./3./4. Biomarkers have helped in our basic molecular understanding of cell transformation, resulting in the identification of new therapeutic targets and novel therapies directed at
Figure 1 Evolution and Broad Applications of Biomarkers in Oncology Precision Medicine 30 Journal for Clinical Studies
Volume 13 Issue 4