The first liquid-biopsy test for tumor DNA gains approval

Historical milestone — this page describes an event dated 2016. It is not current breaking news.

What the FDA approved

On June 1, 2016, the FDA granted premarket approval P150047 to Roche Molecular Systems for the cobas EGFR Mutation Test v2.

The test itself was not new. What was new was the sample. The FDA approval record states that the defined EGFR mutations can be detected using DNA isolated from formalin-fixed paraffin-embedded tumor tissue or from circulating-free tumor DNA in plasma, drawn from ordinary peripheral blood.

That second option is what people mean by a liquid biopsy: reading a tumor's genetics from a tube of blood instead of a piece of the tumor.

Why blood works at all

Tumors shed. As cancer cells die, fragments of their DNA enter the bloodstream and circulate among the far larger amount of DNA shed by healthy cells.

Those fragments are called circulating tumor DNA, often shortened to ctDNA. They carry the same mutations as the tumor they came from. The technical problem is proportion: tumor DNA can be a tiny fraction of what is floating in a blood sample, so the test has to find a small signal in a large amount of noise. The cobas test does this with real-time PCR, a method that copies a targeted DNA sequence over and over until there is enough to measure.

What it was approved to look for

The test is a companion diagnostic, meaning it is formally paired with specific drugs. NCI defines a companion diagnostic as a biomarker test tied to a particular treatment.

From the blood sample, the FDA record ties the test to erlotinib (Tarceva) for two changes in the EGFR gene: exon 19 deletions and the L858R substitution. EGFR stands for epidermal growth factor receptor, a protein on the cell surface that signals the cell to grow. When the gene is altered in these specific ways, the signal is stuck on — and drugs that block EGFR can work.

The approval record also notes that a set of other EGFR mutations the test detects have no established drug safety and efficacy behind them. The test finding something is not the same as the finding being actionable.

The limitation the FDA wrote into the approval

This is the most important sentence on the page, and it comes directly from the approval record: patients who are negative for these mutations on a plasma sample "should be reflexed to routine biopsy and testing for EGFR mutations with the FFPET sample type."

In plain terms, a negative blood test does not settle the question. Some tumors shed too little DNA into the blood to be caught. A negative result sends you back to a tissue biopsy rather than closing the matter.

A positive result is trustworthy. A negative one is incomplete. That asymmetry still applies to liquid biopsies today, and it is the single most misunderstood thing about them.

What made it useful

Lung tumors are awkward to biopsy. Getting tissue can mean a needle through the chest wall, a bronchoscope, or surgery, with real risks and recovery time. Some tumors sit where a needle cannot safely reach, and some patients are too unwell for the procedure.

A blood draw removes that barrier. It can also be repeated. A tissue biopsy captures the tumor once, at one moment; blood can be sampled again as treatment proceeds and the cancer changes.

Where this fits in cancer care now

NCI describes biomarker testing as looking for genes, proteins, and other substances that provide information about a cancer, and notes that each person's cancer has its own pattern. Some targeted therapies and immunotherapies only work in cancers carrying particular biomarkers.

Testing can also open doors to clinical trials. NCI points to basket trials, which enroll people based on the genetic changes in their cancer rather than where in the body it started. Our what cancer is page covers the underlying biology.

NCI is careful to add that precision medicine is not yet routine care for most patients, and that selecting treatment by cancer type, size, and spread remains effective.

Symptoms that should prompt a check

Lung cancer is often found late. SEER reports that only about 24% are caught while still confined to the lung, where five-year relative survival is 65.5%, against 10.5% once the cancer has spread to distant sites.

See a clinician about:

• A cough lasting more than three weeks, or a familiar cough that changes.
• Coughing up blood, at any amount, even once.
• Breathlessness doing things that were easy a few months ago.
• Persistent chest or shoulder pain.
• Hoarseness beyond three weeks.
• Chest infections that keep returning.
• Unexplained weight loss.

Screening is separate and has specific criteria: an annual low-dose CT for adults aged 50 to 80 with a 20 pack-year history who smoke now or quit within 15 years. Our lung cancer page covers what follows an abnormal result.

What to keep in perspective

• A negative blood result does not rule out the mutation. The FDA approval itself directs those patients to tissue biopsy.
• This 2016 approval covered two EGFR mutations in one cancer type. It was not the broad multi-gene blood panel that the phrase "liquid biopsy" now often implies.
• It is a test for choosing treatment in people already diagnosed with lung cancer. It is not a screening test, and it was not approved to find cancer in healthy people.
• Some mutations the test detects have no approved drug attached, so a positive finding does not automatically mean a treatment exists.
• This page summarizes a historical approval. Device labeling and indications change, so check current FDA records rather than this summary.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• U.S. Food and Drug Administration, Premarket Approval P150047, cobas EGFR Mutation Test v2, decision date June 1, 2016: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P150047
• National Cancer Institute, Biomarker Testing for Cancer Treatment: https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment
• SEER Cancer Stat Facts, Lung and Bronchus Cancer: https://seer.cancer.gov/statfacts/html/lungb.html
• U.S. Preventive Services Task Force, Lung Cancer: Screening: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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