Biomarkers have several key roles in clinical trials and precision medicine

Biomarker use in clinicals trials has expanded over the last few decades. Designing a protocol that incorporates biomarkers can reduce trial timelines and increase the chance of success. However, biomarkers remain underutilized for a variety of reasons. Evaluating the trends in biomarker use allows us to monitor the effectiveness of new strategies and identify areas of opportunity.


We have observed considerable progress in the use of biomarkers to account for patient genetic variability for trial recruitment, segmentation, disease monitoring and therapeutic efficacy in the life sciences industry over the past three decades. In a new report, Biomarker-driven efficiencies in clinical trials: Insights from the evolution of precision medicine, we use historic data from this time period to provide insights into the evolution and future of biomarker use in clinical trials and precision medicine.


Increasing adoption of precision medicine

At the very basic definition, precision medicine provides the information about what drug to prescribe, at what dose and when, for which patient. This approach may eventually replace the trial and error associated with the traditional “one-size-fits-all” model for development and prescription of treatments. Data have highlighted the heterogeneity that affects how individuals respond to medications, because of differences in absorption, metabolism, excretion and drug therapy target.


Precision medicine focuses on individual variations in genetics as well as differences in environments and lifestyles that will affect the efficacy and safety of a given treatment.

With a shift toward a more personalized model, we gain efficiencies throughout the drug development lifecycle (by designing trial protocols that include only those patients most likely to respond) to the clinic (where better care can be provided to the patients in need of treatments).


Informing therapy and clinical trial recruitment decisions with biomarkers in oncology

In oncology, there is a long history of incorporating biomarkers, which have become more sophisticated over the years, for diagnostic, therapeutic and prognostic purposes (Figure 1).


Figure 1. Trends in the use of biomarkers for oncology therapy and research.
Source: Cortellis Drug Discovery Intelligence™


Herceptin (trastuzumab), a monoclonal antibody, was one of the first targeted cancer therapies to be approved by the FDA in 1998 as treatment for HER2-positive metastatic breast cancer as combination first-line therapy and on its own as second-line therapy. Therapeutic mechanisms are also closely linked to the biomarkers HER2, EGFR, KRAS, BRCA1/2 and PD1/PD-L1 for cancers such as breast cancer, non-small cell lung cancer and ovarian cancer.


Herceptin was one of the first FDA-approved targeted cancer therapies for HER2-positive breast cancer.


The field of toxicogenomics is also beginning to support the early assessment of the influence of gene variants on the risk for adverse events, which would help determine the maximum tolerated dose for a given individual as well as the specific patient subsets that might develop potentially toxic side effects.

A well-known example of the influence of genetic variability on drug-induced adverse events is the observed cardiotoxicity in women receiving doxorubicin chemotherapy, which is exacerbated when used in combination with trastuzumab.1 For more information on this topic, refer to the recent Clarivate report, Best practices in toxicology: Current perspectives for enhancing drug safety.


Shortening clinical trial timelines

Designing a protocol that uses biomarkers to inform patient recruitment or to stratify patients during enrollment can decrease the required sample sizes and chance of adverse events, reducing the time to get the drug to market and increasing the success rates. This is especially true for oncology trials, for which the probability of success increases to 10.7% with biomarker-led stratification compared with 1.6% without biomarker-led stratification.2

For example, crizotinib, an oral ALK inhibitor, was approved to treat ALK-positive non-small cell lung cancer (NSCLC) only three years after the ALK rearrangement was reported as a target in lung cancer (Figure 2).3 In addition, ceritinib, another ALK inhibitor, was granted accelerated approval after phase I testing (42.7 months) as second-line treatment in patients with ALK-positive NSCLC after treatment with crizotinib.4


Figure 2. Time to market from initial identification of a specific drug target.
Source: Nature Medicine 17(3): March 2011 BCR-ABL inhibition Gleevec.

Leveraging data for greater insights and faster time to market

Oncology has been the leading therapeutic area in terms of biomarker development and use, setting the stage for biomarker adoption in other therapeutic areas. This includes new and adaptive designs focused on precision medicine. However, as we discuss in our recent report, Biomarker-driven efficiencies in clinical trials: Insights from the evolution of precision medicine, biomarker use is still being underutilized in clinical trials. Opportunity remains to incorporate biomarkers, and particularly biomarker-based stratification, into clinical trials — to shorten trial durations and increase the chances of successful outcomes.

As the industry continues its effort to speed much-needed new therapies to market, evaluating the trends over time allows us to monitor the effectiveness of new strategies and identify where the industry still has room to expand. Access Cortellis Drug Discovery Intelligence and Cortellis Clinical Trials Intelligence™ for the broadest, deepest, most accurate sources of R&D and clinical trial planning intelligence.




  1. Schneider BP, Shen F, Gardner L, et al. Genome-Wide Association Study for Anthracycline-Induced Congestive Heart Failure. Clin Cancer Res. 2017;23(1):43-51.
  2. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2): 273–286. doi: 1093/biostatistics/kxx069
  3. Gerber DE, Minna JD. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell 2010;18(6):548-551. doi: 10.1016/j.ccr.2010.11.033
  4. Dhillon S, Clark M. Ceritinib: first global approval. Drugs 2014;74:1285-1291.