Treatment of cancer first starts from the diagnosis stage to determine the right drugs and therapy for each patient. Biopsies are the most common diagnostic tool for identifying cancer types and specific mutations. In this interview, we hear from Dr Steven Olsen, CMO at Guardant Health AMEA to learn more about liquid biopsies and its applications as a cancer diagnostic tool and possibly tracking of cancer progression.
1. What are the key benefits of liquid biopsies over tissue biopsies when it comes to cancer genotyping?
In order to make the diagnosis of cancer, it is essential to obtain a sample of the tumour tissue. However, after the initial diagnosis is made, additional tests may be needed to characterize the cancer and to determine the most appropriate treatment. Some of these tests involve analysing the genetic profile of the cancer. This can be done with tissue, if there is enough remaining. However, there is another option. Because small amounts of cancer DNA can be released into the bloodstream, a blood test or “liquid biopsy” can also be used to identify genetic changes from the cancer. This approach offers several advantages over tissue when it comes to cancer genotyping.
Our flagship liquid biopsy, Guardant360®, can provide results within approximately 7 days upon sample receipt in our laboratory. Blood samples can be shipped from 41 countries in Asia, the Middle East, and Africa. On the other hand, comprehensive tissue genotyping may require 4 weeks or longer. Receiving results faster means that patients can start the most appropriate treatment sooner.
Furthermore, a comprehensive liquid biopsy such as Guardant360® can provide information on many genetic alterations with just one test. Our assay includes an array of relevant genomic biomarkers that are recommended for testing by international guidelines, such as those from the U.S. National Comprehensive Cancer Network (NCCN). Sometimes tissue samples are tested for one genetic alteration at a time. Not only does this potentially take longer, but the supply of tumour tissue may run out before all recommended tests can be completed. Incomplete testing may lead to inappropriate treatment.
An important limitation of a tissue biopsy is that it can inform a physician only about that specific portion of the tumour from which the sample was collected. Some parts of the same tumour mass may have slightly different genetic profiles. Therefore, a single biopsy from only one part of the tumour may miss this diversity. However, because cancer cells from all parts of the tumour can release their DNA into the bloodstream, a liquid biopsy can detect all of that variety in a single test.
When tumour tissue from the original biopsy is no longer available, an additional invasive biopsy may be recommended. However, such procedures delay treatment, are associated with potential complications, and may not always yield sufficient tumour tissue. Considering the time to schedule the biopsy and return results, Guardant360® is faster, avoids invasive procedures, and can provide complete testing with just two test tubes of blood (10mL each) from the patient.
2. What are some reasons for tissue biopsy to still be selected over liquid biopsy?
Tissue biopsies are needed to make the diagnosis of cancer. When there is sufficient remaining tumour tissue from such procedures, labs can quickly proceed to analysis of genetic biomarkers. This is convenient for the patient, who does not necessarily need to return to the clinic for further diagnostic procedures.
However, in cases when there is insufficient tumour tissue for additional tests, some patients are asked to return for another invasive procedure to collect more tissue. Why? Mainly out of habit. The earliest studies of cancer treatments that targeted genetic changes enrolled patients based on tissue tests, because that was the only option available at the time. Subsequently, tissue testing became known as “the gold standard,” even though tissue genetic testing, like any diagnostic procedure, is imperfect.
Since those early days, new technologies have emerged that provide an alternative and equally effective approach. For example, in prospective clinical studies that compared the performance of traditional tissue testing methods, advanced sequencing of tumour DNA in blood (liquid biopsy) identified actionable biomarkers just as well -- and significantly faster.
3. Which types of cancers are most researched for validation of liquid biopsy use?
From Guardant Health’s experience, the most common use of liquid biopsy is in advanced stage solid tumours that are most likely to harbour informative genomic biomarkers. These include lung adenocarcinoma, colorectal cancer, stomach cancer, and breast cancer.
4. Further to bring a diagnostic tool, what other potential possibilities can liquid biopsies provide in relation to cancer progression and relapse?
Liquid biopsies are not yet to the stage where they can diagnose cancer in lieu of a tissue biopsy. However, they are currently being used primarily to identify genetic biomarkers that can guide therapy selection. The convenience of liquid biopsies allows for tumour genetic profiling even after initial cancer treatment stops working. Liquid biopsies have been shown to identify new genetic mutations that are susceptible to different medicines. This can be done without the need for another invasive biopsy.
5. How have the efforts of Guardant Health AMEA help support the push toward validation of liquid biopsies?
Our company is committed to sharing the latest advances on the appropriate clinical application of our products and in providing clinicians and patients the confidence to select our diagnostic tests for making treatment decisions. We partner with pharmaceutical companies and support academic research conducted by leading investigators throughout Asia and the Middle East. Data using Guardant Health’s liquid biopsies have appeared in hundreds of presentations at international scientific conferences and in over 200 peer-reviewed publications. For example, results from Guardant Health research conducted in the AMEA region have appeared in JCO Precision Medicine, JTO Clinical Research Reports, Nature Medicine, and The New England Journal of Medicine. No other liquid biopsy has such a deep library.
6. What is Guardant360® liquid biopsy?
The Guardant360® assay is Guardant Health’s breakthrough liquid biopsy that provides fast, accurate and comprehensive genomic results from a simple blood draw in approximately seven days upon sample receipt in the laboratory. It is used for advanced stage cancer patients with solid tumors. This test uses next generation sequencing (NGS) technology to analyse circulating tumour DNA (ctDNA), small fragments of genetic material that are released from cancer cells.
The assay interrogates 74 clinically relevant genes at one time, and tests for genetic abnormalities recommended by international cancer treatment guidelines. The Guardant360® results are used by physicians to make appropriate treatment decisions regarding the use of precision medicine. In August 2020, the U.S. Food and Drug Administration (FDA) approved Guardant Health’s companion diagnostic, the Guardant360® CDx test, for comprehensive tumor mutation profiling across all solid cancers, making it the first comprehensive liquid biopsy to receive such approval.
7. How can Guardant360® enable acceleration of clinical trial enrolment?
Findings from the GOZILA study in Japan, published in Nature Medicine, showed that nearly twice as many patients could be enrolled into clinical trials based on Guardant360® liquid biopsy results compared to advanced tissue biopsy results. Furthermore, patients could be enrolled 3 times more quickly, in part due to the shorter turnaround time for results. Most importantly, treatment outcomes were no different for patients enrolled into studies of targeted therapies based on Guardant360® results compared to those enrolled based on tissue testing results.
About the interviewee
Dr Steven Olsen MD, PhD, is currently the Chief Medical Officer for Guardant Health AMEA. He is a medical oncologist with 20 years of experience in drug and diagnostics development and medical affairs. He received a BS in Biological Sciences from Stanford University, an MD from Oregon Health and Science University, and a PhD in Cellular and Molecular Biology from the University of Michigan. He completed post-graduate training at the University of California, San Diego, and at the University of California, San Francisco. He has held various positions of increasing responsibility at Sanofi, Genentech, and AstraZeneca. He led global development on medical strategy for anti-cancer medicines such as Taxotere, Kadcyla, Faslodex, Lynparza, and Tagrisso.