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The role of biomarker testing in treatment decision making: Current and future perspectives

Prof Ahmad Awada is Head of Oncology Medicine Department at the Jules Bordet Institute, Brussels, Belgium, and specialises in the treatment of solid tumours. Prof Awada takes an active role in drug development and spoke to EMJ about the use of genomic biomarkers in today’s oncology landscape and their impact on treatment decision-making.

Q: How important is testing for genomic biomarkers in today’s oncology treatment? How does it support your treatment decisions and what is the direct impact on patients?

Information regarding tumour biomarkers helps further the understanding of tumour biology and is important in clinical decision making. Whilst today, still only a fraction of oncology patients can benefit from targeted therapies their role and that of biomarker data will be increasingly significant in future oncology treatment landscape. It is important to note that currently, many patients are unable to access targeted therapies due to reimbursement and market access restrictions. Whilst the technology is developing at an increasing pace and number of clinical trials evaluating targeted therapy is growing, the regulatory and economical groundwork needs to be in place for all patients to be able to access these therapies.

Q: Do you feel that the oncologist community has enough information about biomarker testing?

The knowledge of biomarkers differs. Some are well known, such as EGFR, BRAF, and ROS1, whereas the value of others is less clear. Whilst it is important to understand and be familiar with the latest developments in biomarkers and associated therapies, I am unsure if all oncologists have similar levels of expertise and understanding. Furthermore, and unfortunately, oncologists outside major cancer centres may not have the needed the information regarding biomarkers or have access to targeted therapies and must rely on the standard of care (SoC). Thus, the practice of biomarker identification to inform treatment decision making differs between academic and comprehensive cancer centres and the rest of the oncology community, which is not ideal situation for patients.

Q: What is the clinical value for the oncologist and patients in receiving all biomarker test results (package) at the same time compared with receiving the biomarker information sequentially?

Personally, I will order full panel analysis to receive all the biomarker data at the same time. This is beneficial for patients because I can enrol the patient onto a clinical trial if there are no licensed, targeted therapies available. In general hospitals, this is not typically the case and sequential testing is still common or patients tend to be treated with the SoC and referred later for enrolment onto a clinical trial if the response is suboptimal; this delay is not favourable for patients.

In terms of timing, it is better for both the patient and the physician to receive all the biomarker analysis data at once, instead of waiting for the subsequent data in cases where the initial biomarker results are negative. Sequential biomarker testing may be associated with further delays before treatment initiation.

Q: Biopsies are often very small and, increasingly, fine needle aspirations (FNA) are the only samples available. How does that impact patient care?

Yes, this is a problem, particularly for patients with NSCLC because the quantity of tissue available for analysis is small. There may be problems associated with sequential testing if the findings from the initial analysis are negative and there are not enough samples available for further testing. Oncologists then do not have the required information and patients may not be able to receive targeted therapy from which they could benefit. Liquid biopsies have the potential to help overcoming this problem.

Q: Different testing methods might require different amount of tissue sample, does that play a role?

The preference would be if the laboratory was able to use smaller quantities of tissue to produce good quality results. However, it is important to optimise sampling to achieve the best biomarker test results and clinicians should always strive to provide sufficient sample.

Q: Do you think the lab should be performing the panel testing in a reflex manner in cases of NSCLC following the standard histological diagnosis, without additional request from the clinician?

Yes, I am in favour of laboratories performing panel testing in a reflex manner without additional request from clinicians. Some pathologists and molecular biologists in the hospital are familiar with undertaking panel tumour biomarker analysis and assist the oncologist with the selection of targeted therapy accordingly. For example, there are three or four biomarkers that should automatically be part of routine testing without a request from the physician. Currently, physicians are asking pathologists what biomarker analysis they think needs to be performed. The pathologists and molecular biologists are a very important part of the team.

Q: What is the ideal turnaround time to return complete results for all the biomarkers that you can potentially action? What is the potential impact on the patient if there is a delay in obtaining the biomarker test results?

It is important to have all the actionable biomarker information as early as possible. However, I am aware that biomarker analysis is not a simple procedure. It is important to have valuable, reliable results, but clinicians also need to be realistic. Up to 2 weeks is usually the acceptable time frame, but the sooner the better. Patients may have already waited a considerable length of time while undergoing biopsy and diagnosis and the time before treatment initiation following biomarker analysis may be 3–4 weeks which might be not optimal.

Q: Should the result report include just the biomarker details or also information regarding available targeted therapy and ongoing clinical trials to best help you in making your management decisions?

There are some well-known biomarkers, such as EGFR, where the treatment choice is very clear, and most oncologists can easily make an informed decision. However, for the less well-known biomarkers, including those being assessed in clinical trials, additional information would be valuable.

Q: Do you think this trend of associating more biomarkers with routine treatment is going to continue?

Yes, definitely. Currently, only about 10% of patients benefit from targeted therapy, but this varies according to the tumour. Testing is becoming increasingly available but access to targeted therapies is problematic. Physicians are already asking for more biomarker analysis and this trend will continue. I foresee that in 3–5 years approximately 20–25% of patients will benefit from precision medicine. It is important to note that even once these therapies have been developed, not all patients will be able to access and receive targeted therapy due to delays or restrictions in access and reimbursement.

Q: Is in-house testing or sending out to large service labs preferable for biomarker analysis?

Common biomarkers, such as EGFR, ALK, BRAF, and ROS1, should be identified by in-house laboratories. Large service or reference labs may be preferential for rare or new biomarker analysis to ensure optimal patient enrolment onto clinical trials. In any case, the most important factors are the quality of the results and the ability to produce data quickly.

Q: Do you discuss a patient’s biomarker analyses with the tumour board?

Yes. Although we are unable to discuss all patients due to time constraints, we are able to select a handful for discussion. During these sessions the biomarker report is helpful.

To conclude, the use of biomarkers and associated precision medicine is not a simple topic, and whilst patients are and will clearly benefit from targeted therapy, not all patients have or will have access to these therapies.  Currently, technology is moving at a very fast pace, and we are able to identify biomarkers to guide therapeutic decision making for the selection of targeted medicines. Nevertheless, there is a considerable gap in how this is practised in the oncology community. This gap can be closed through multiple means, such as medical education, interaction between labs and physicians, and importantly improved access to new therapies. The proportion of patients who will benefit from precision medicine will increase in the future. Currently it is not the answer for all patients, but the pace of development is accelerating.