FDA Approves First Liquid Biopsies That Test for Mutations in Multiple Genes

Drawing of circulating tumor DNA
Image credit: Jonathan Bailey, NHGRI
Medically Reviewed by Expert Board

This page was fact checked by our expert Medical Review Board for accuracy and objectivity. Read more about our editorial policy and review process.

This article was last modified on

The Food and Drug Administration (FDA) recently approved new tests to detect DNA circulating in the blood after being shed by cancerous tumors. These tests use advanced testing technology to provide genetic information about the tumors and tell whether specific cancer drugs may treat them.

In recent years, cancer drugs have been developed to target specific genetic changes (mutations) in tumors. Testing the tumor for the particular mutation that the drug targets can help predict who may benefit from the drug and who is not likely to respond.

Most often, this genetic testing is done on tumor tissue collected during a traditional tissue biopsy that involves removing small pieces of tumor tissue through surgery, or in some cases a needle biopsy. The newly approved tests are blood tests and are commonly called liquid biopsies. They may be used alongside or as an alternative to invasive tissue biopsies. In general, liquid biopsies detect circulating free DNA or whole cells shed by tumors into the blood and require only a blood sample. They are especially useful when the location of a tumor makes it difficult or impossible to remove a sample for analysis. While tissue biopsies are the standard of care for diagnosing cancer, liquid biopsies may be acceptable for more frequent sampling to monitor cancer and guide treatment.

Until now, the liquid biopsy tests approved by the FDA could identify specific changes in single genes only. The two newly approved tests use a technique called next-generation sequencing (NGS), which can evaluate many different genes at the same time. By combining two powerful technologies—liquid biopsy and NGS—the new tests more easily provide enhanced genetic information about tumors and help determine whether targeted cancer drugs can be used to treat the tumors.

The FDA approved both tests in August 2020 for patients with advanced cancer in whom certain treatments are being considered. The tests are made by two different companies and were approved separately. The first test finds changes in 55 tumor genes. It was specifically approved as a companion diagnostic (a test that identifies whether patients are good candidates to receive specific drugs) for patients with a type of non-small cell lung cancer (NSCLC) to detect mutations in the EGFR gene that may respond to a drug called osimertinib. The test also provides information on mutations in other genes, such as KRAS and BRAF, which can also influence treatment planning.

The second test looks for mutations in 324 genes. It was approved as a companion diagnostic for drugs used to treat advanced metastatic prostate cancer with BRCA1 and BRCA2 mutations and NSCLC with EGFR mutations. In late October and early November 2020, the FDA expanded approved use of the second test to include additional targeted drugs and mutations related to advanced breast and ovarian cancers, NSCLC, and metastatic prostate cancer. In addition to its potential to identify patients who may benefit from targeted therapies, the second test also helps identify patients who might benefit from treatments that boost their natural immune systems to fight cancer (immunotherapy).

Besides ease of sampling, another advantage of liquid biopsy tests is that results are generally available more quickly than results from standard tissue biopsies. Liquid biopsies may also be used to see if therapy is working. They can be repeated easily and more frequently to see whether tumor DNA is disappearing from the blood. Because results are returned more quickly than those of standard biopsies, liquid biopsies may make it simpler to switch to a different therapy when the initial treatment is not working.

While both tests represent a major advance in cancer care, liquid biopsies are relatively new, and their use involves several important considerations. These issues include questions about the potential for false-positive results and how to use negative results and information about mutations in genes for which there are no targeted therapeutics. Additionally, these tests may not detect mutations that are present in the tumor if the tumor isn’t shedding enough DNA into the blood. For this reason, the FDA says that patients who get negative results with a liquid biopsy should also have a tissue biopsy for traditional molecular testing.

Although the FDA approved these tests for use only in advanced cancer patients, researchers and companies are developing more liquid biopsy NGS tests that may eventually help other cancer patients. These tests could show whether cancer cells remain after treatment and if cancer has returned. Other future tests could find cancer at early stages and may one day serve as screening tests. At least three companies are currently developing tests for these applications. While liquid biopsies continue to become commercially available, more research is needed to understand the benefits and limitations of these tests.

View Sources

Deborah Levenson. A New Era for Liquid Biopsy. Clinical Laboratory News. Available online at https://www.aacc.org/cln/articles/2020/november/a-new-era-for-liquid-biopsy. Published November 1, 2020. Accessed January 5, 2021.

Press release. FDA Approves First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test. Food and Drug Administration. Available online at https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test. Updated August 11, 2020. Accessed January 5, 2021.

Press Release. FDA approves liquid biopsy NGS companion diagnostic test for multiple cancers and biomarkers. Available online at https://www.fda.gov/drugs/fda-approves-liquid-biopsy-ngs-companion-diagnostic-test-multiple-cancers-and-biomarkers. Updated November 9, 2020. Accessed January 5, 2021.

Taylor Soper. Bill Gates and Jeff Bezos-backed cancer detection company Grail, led by ex-Juno CEO, files for IPO. Geek Wire. Available online at https://www.geekwire.com/2020/bill-gates-jeff-bezos-backed-cancer-detection-company-grail-led-ex-juno-ceo-files-ipo/#:~:text=Cancer%20detection%20startup%20Grail%20today,A%20round%20four%20years%20ago. Published September 9, 2020. Accessed January 5, 2021.

Joel Berg. String of FDA approvals gives momentum to liquid biopsies. MedCity News. Available online at https://medcitynews.com/2020/11/string-of-fda-approvals-gives-momentum-to-liquid-biopsies/. Published November 4, 2020. Accessed January 5, 2021.

Associated Press. Experimental blood test detected many types of cancer in early stages, company says. USA Today. Available online at https://www.usatoday.com/story/news/2019/05/31/blood-tests-detect-cancer-grail-inc-liquid-biopsy/1297048001/ . Published May 31, 2019. Accessed January 5, 2021.

Conor Hale. Grail’s cancer blood test tracks down over 50 types of early-stage disease in study. Fierce Biotech. Available online at https://www.fiercebiotech.com/medtech/grail-s-cancer-blood-test-tracks-down-over-50-types-early-stage-disease-study. Published March 31, 2020. Accessed January 5, 2021.

(September 15, 2020) FDA Approves Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test. Available online at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test. Accessed January 5, 2021.

(November 10, 2020) FDA Approves Liquid Biopsy NGS Companion Diagnostic Test for Multiple Cancers and Biomarkers. ESMO. Available online at https://www.esmo.org/oncology-news/fda-approves-liquid-biopsy-ngs-companion-diagnostic-test-for-multiple-cancers-and-biomarkers. Accessed January 5, 2021.

(September 1, 2020) FDA Approves Two Liquid Biopsy Tests, Fight CRC. Available online at https://fightcolorectalcancer.org/blog/liquid-biopsy-tests/ . Accessed January 5, 2021.