In 1958, the first tumor biomarker was discovered when the estrogen receptor was identified in breast cancer.¹ Since then we have been chasing the promise of precision oncology. Today, we are in the heyday of biomarker discovery, utilization, and translation to clinical practice.

Increasingly, tumor biomarkers, which include gene mutations, gene fusions, and protein overexpression, are used to direct patients to treatment with FDA-approved targeted therapies. As we continue to divide cancers by their biomarker profile into subsets, what we defined as common diseases for a general population have become more distinctly rare diseases for specific populations. This changes the way that we, as clinicians, must think about oncology treatment.

Using Biomarker Data to Advance Precision Oncology

Although this segmentation of common diseases into multiple patient populations with different treatment targets presents challenges for drug development and managing clinical use, it is critical to identify patients for targeted therapies because it translates into better care. This process is made more difficult because we can’t find those patients if they are not being tested and clinicians don’t have ready access to biomarker data.

Precision oncology is focused on predicting which patients are likely to respond to specific treatments as well as optimizing access to individualized treatment. The availability of biomarker results with detailed information about biomarker performance and disease association is critical to building the evidence-based precision oncology data source needed to guide clinical practice.

Impact on Patient Care

Identifying a tumor’s biomarkers and combining it with clinical information can also help expand participation in real-world evidence (RWE) studies that provide insights to inform patient care. Biomarker data also open the door to new clinical research opportunities examining new targeted therapies with new trial designs for rare diseases with smaller patient groups, with the potential result of faster translation to treatment options.

In the case of non–small-cell lung cancer (NSCLC), we can look at patients with different alterations. For example, although NSCLC is common, only approximately 3% of patients with NSCLC have a specific activating HER2 mutation. This led to the investigation of this patient subset with a novel therapy and the subsequent accelerated FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) for adults with NSCLC with HER2 mutation.²

Biomarker data may also help restratify patients in terms of treatment options. Although a patient may not have an actionable biomarker in the first-line setting, reevaluating the biomarker status may prove beneficial.

For example, in the phase 3 CodeBreak 200 trial (NCT04303780), the KRAS G12C inhibitor sotorasib (Lumakras) doubled the rate of progression-free survival at 12 months and reduced the risk of disease progression compared with standard second-line therapy for patients with previously treated NSCLC and KRAS G12C mutations.³

Integrated biomarker and clinico-genomic data will power early-stage drug development with longitudinal treatment and outcomes data while providing additional RWE applications, including as follows:

• Evaluating novel targets and understanding expression levels of a cancer target

• Identifying biomarkers and new target indications • Identifying patients for clinical trials

• Designing clinical trials based on biomarkers

• Linking genomics data to other clinical factors to predict response

For example, in BRAF-mutated colorectal cancer and HER2-positive gastric cancer, assessment of patient biomarker data at the point of care may lead to more personalized and effective care:

• With poor prognosis associated with BRAF V600E mutations, studies are underway to determine mechanisms of resistance to standard therapies, which may lead to the development of novel treatment options.⁴

• The benefits of targeted therapy to treat patients with HER2-positive breast cancer are proven. There is growing understanding that HER2 is also overexpressed in other forms of cancer, including gastric cancer. The discovery of HER2-positive gastric cancer has prompted a number of studies, and it is expected that more anti-HER2 drugs will be developed and introduced into clinical practice to treat patients.⁵

How to Incorporate Biomarkers Into Routine Care

Access to these new treatments for rare diseases and newly segmented patient populations is expanding rapidly. In order to fully leverage the clinical impact of precision oncology, clinicians must incorporate biomarker testing as part of routine care and practice in order to facilitate treatment selection and reimbursement.

With the rapid pace of biomarker discovery and development of biomarker testing options and novel targeted treatments, how can clinicians best keep up to date?

Journals such as this one can provide valuable information; however, many of us do not have time to read as many papers as we would like.

An alternative is an oncology-specific electronic health record (EHR) that provides decision support tools to help match each patient to the right evidence-based treatment option. Ontada’s iKnowMed EHR enables clinicians to utilize standardized up-to-date care guidelines based on the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology.

Developed in collaboration with oncologists to optimize workflow, the system also features a built-in biomarker ordering guide. This automatically updates clinicians to pathways and guidelines as new evidence emerges. Covering more than 30 primary oncology tumors with detailed recommendations by subtype (stage, histology, biomarker status, etc), access to biomarker data at the point of care enables more personalized and effective care for patients.

Used solely for oncology patients, the iKnowMed EHR captures outpatient medical histories from community oncology practices nationwide. Through use of a shared EHR platform, clinicians are able to use this information to perform research in collaboration with other oncologists and life sciences companies, providing the opportunity to answer important questions that are relevant for drug development as well as for informing clinical practice.

Precision Oncology: The New Reality

We have been talking about the promise of precision oncology for years, and it has finally arrived and can be utilized in daily patient care. As more biomarkers and targeted treatment options are approved and transitioned into clinical practice, precision oncology is the new reality for oncologists and patients.

Proactive biomarker testing for managing patient care and gathering RWE data is critical to continue building the evidence base in precision oncology needed to improve patient outcomes for even more patients with new and/or rare diseases.

REFERENCES

1. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol. 2019;116:135-170. doi:10.1016/bs.apcsb.2019.01.001

2. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. News release. Updated August 16, 2022. Accessed April 6, 2023. http://bit.ly/3KDvOIz

3. Johnson ML, de Langen AJ, Waterhouse DM, et al. Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study. Ann Oncol. 2022;33(suppl 7):S1417-S1418. doi:10.1016/annonc/annonc1089

4. Ciombor KK, Strickler JH, Bekaii-Saab TS, Yaeger R. BRAF-mutated advanced colorectal cancer: a rapidly changing therapeutic landscape. J Clin Oncol. 2022;40(24):2706- 271

5. doi:10.1200/JCO.21.02541 5. Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17(1):1-12. doi:10.1007/s10120-013-0252-z