FDA Expands Guardant360 CDx Use to Match Cancer Patients With Targeted Therapies

The U.S. Food and Drug Administration has authorized multiple uses of Guardant360 CDx as a companion diagnostic, allowing blood-based genomic testing to identify specific cancer mutations linked to certain targeted treatments. The test analyzes circulating cell-free DNA from blood and has expanded indications across cancers including non-small cell lung cancer and breast cancer. In 2026, FDA authorizations added further treatment-matching uses, including biomarkers linked to therapies for HER2-mutant lung cancer and ESR1-mutated breast cancer.

Cancer treatment is increasingly moving away from a one-treatment-fits-all approach.

Two patients may have the same broad type of cancer while carrying different genetic changes inside their tumors. Those differences can influence whether a particular targeted medicine is appropriate.

That has created a growing role for companion diagnostics — tests designed to identify biological characteristics that can help determine whether a patient may benefit from a specific therapy.

One of the technologies at the center of this shift is Guardant360 CDx, a blood-based genomic test developed by Guardant Health. Rather than requiring every cancer-related genetic analysis to begin with a tissue biopsy, the test can examine DNA fragments circulating in a patient’s blood.

The FDA has authorized Guardant360 CDx for multiple treatment-selection indications, expanding its role in precision oncology.

How Guardant360 CDx Works

Tumors can release fragments of DNA into the bloodstream. These fragments are known as circulating tumor DNA, or ctDNA, and form part of the broader pool of circulating cell-free DNA found in plasma.

Guardant360 CDx uses next-generation sequencing to analyze genetic alterations in this circulating DNA.

The technology can identify specific mutations and other genomic changes that may be relevant to cancer treatment.

The important point is that the test does not simply report that a mutation exists. For approved companion-diagnostic uses, the result can help identify patients whose tumors contain a biomarker associated with a particular FDA-authorized targeted therapy.

In other words, the test becomes part of the treatment-selection process.

The FDA describes Guardant360 CDx as an in-vitro diagnostic device that uses targeted high-throughput sequencing to detect multiple categories of genomic alterations. Its 2026 Guardant360 Liquid CDx authorization covers detection across hundreds of genes and specifies its use as a companion diagnostic for particular targeted therapies.

From Lung Cancer to Breast Cancer

Guardant360 CDx has accumulated multiple FDA-authorized indications over several years.

In 2021, the FDA expanded the test’s use to detect the KRAS G12C mutation in patients with non-small cell lung cancer. The result could help identify patients who may be eligible for treatment with sotorasib.

The test has subsequently been used for additional biomarkers.

For example, the FDA authorized Guardant360 CDx in 2026 as a companion diagnostic for HER2 (ERBB2) activating mutations in certain patients with non-small cell lung cancer who may be eligible for zongertinib.

The technology has also become increasingly relevant in breast cancer.

In May 2026, the FDA approved Guardant360 CDx as a companion diagnostic for vepdegestrant in adults with ER-positive, HER2-negative advanced or metastatic breast cancer whose tumors contain specified ESR1 mutations.

The FDA’s companion-diagnostic database also lists Guardant360 CDx for additional breast-cancer treatment-selection applications involving ESR1 mutations.

Why a Blood Test Matters

Traditional cancer genomic testing often relies on a tissue sample obtained through biopsy.

Biopsies can provide valuable information, but obtaining tumor tissue can sometimes be difficult because of the tumor’s location, the patient’s condition or the availability of sufficient tissue.

A liquid biopsy offers another source of genomic information.

With Guardant360 CDx, a blood sample can be processed to obtain plasma and analyze cell-free DNA. This makes the approach less dependent on collecting a fresh tumor sample for every genomic assessment.

However, a blood test is not automatically equivalent to a tissue biopsy.

The FDA’s current labeling for Guardant360 Liquid CDx specifically notes that a negative plasma result does not necessarily mean the patient’s tumor lacks the relevant genomic alteration. When appropriate, patients with negative plasma findings may need tissue-based testing.

That limitation is critical because the amount of tumor-derived DNA circulating in blood can vary between patients and cancer types.

What “Precision” Means in Precision Oncology

The term precision medicine can sometimes sound as though a test can determine the perfect treatment for an individual patient.

In reality, genomic testing provides one important layer of information.

A patient’s treatment decision may also depend on cancer stage, previous therapies, overall clinical circumstances, tumor characteristics, laboratory findings and other factors.

Guardant360 CDx is therefore better understood as a tool that can identify particular molecular features relevant to specific FDA-authorized treatments.

For example, if an approved companion diagnostic detects a qualifying mutation, that result can help determine whether the corresponding targeted therapy should be considered under its approved indication.

The test does not independently prescribe treatment or replace clinical judgment.

A Growing List of Biomarker-Therapy Matches

The FDA’s companion-diagnostic database illustrates how quickly this field is expanding.

As of 2026, Guardant360 CDx and Guardant360 Liquid CDx appear in multiple FDA-authorized companion-diagnostic indications involving biomarkers such as KRAS, EGFR, HER2/ERBB2, BRAF and ESR1, depending on the cancer type and therapy.

The FDA authorized Guardant360 CDx in September 2026 for another ESR1-related indication associated with camizestrant in combination with a CDK4/6 inhibitor for certain patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer.

These additions demonstrate an important trend in oncology: the diagnostic test and the drug are increasingly being developed as connected components of treatment.

Instead of asking only, “What type of cancer does the patient have?” clinicians can also ask, “What molecular alteration does this tumor carry, and is there an approved therapy designed around it?”

The Technology Behind the Test

Guardant360 Liquid CDx uses targeted next-generation sequencing rather than examining the entire genome indiscriminately.

The FDA’s May 2026 authorization describes a test capable of detecting single-nucleotide variants and insertions or deletions across 741 genes, copy-number amplifications in two genes, copy-number loss in one gene and rearrangements in nine genes.

That breadth gives the test value beyond individual treatment-selection decisions.

Its genomic findings can also contribute to broader tumor mutation profiling when interpreted by qualified healthcare professionals alongside clinical information and professional oncology guidelines.

But the presence of a genomic alteration does not automatically mean that an FDA-approved targeted treatment exists for that alteration.

The FDA specifically states that genomic findings outside the listed companion-diagnostic indications are not prescriptive or conclusive for the use of a specific therapeutic product.

Liquid Biopsy Is Not the End of Tissue Testing

The rise of blood-based cancer testing does not mean tissue biopsy is becoming obsolete.

Tumors can be genetically heterogeneous, meaning different parts of the same cancer may contain different molecular characteristics.

In addition, some tumors release relatively little DNA into the bloodstream.

For that reason, a negative liquid-biopsy result may require follow-up testing using tissue when clinically appropriate.

This combination of liquid and tissue testing is likely to remain important as precision oncology becomes more sophisticated.

Blood testing can offer a convenient way to repeatedly examine tumor-derived genetic information, while tissue can provide direct information about the tumor’s cellular and molecular environment.

What This Means for Cancer Treatment

The significance of technologies such as Guardant360 CDx lies in their ability to connect molecular information with treatment decisions.

Targeted cancer drugs are generally designed around particular biological pathways or molecular alterations. If the relevant alteration can be identified through a validated diagnostic test, clinicians have a clearer basis for determining whether the corresponding therapy may apply.

The FDA’s recent authorizations show this relationship becoming increasingly specific.

In 2026 alone, Guardant360-related authorizations expanded into additional treatment-selection scenarios involving breast and lung cancer biomarkers.

This is a broader shift in oncology: the diagnostic test is becoming part of the treatment architecture itself.

The Remaining Challenges

Despite the progress, precision oncology still faces significant limitations.

Not every tumor contains an actionable mutation. Not every actionable mutation has an approved treatment. And even when a patient has the biomarker associated with a targeted therapy, treatment response can vary.

Cancer can also evolve during treatment.

A mutation that was not detectable at one stage may become more prominent later, while resistance-associated changes can emerge under treatment pressure.

Repeated genomic monitoring through blood-based testing could potentially help researchers and clinicians study these changes, although the appropriate use of testing depends on the specific cancer, therapy and clinical setting.

There are also questions surrounding cost, accessibility, interpretation and the growing volume of genomic information generated by modern sequencing platforms.

The Next Phase of Precision Oncology

The development of companion diagnostics represents a deeper change in how cancer is classified and treated.

The future of oncology is increasingly likely to involve a combination of pathology, imaging, clinical history and molecular information rather than relying on a single diagnostic measurement.

Blood-based genomic tests are one component of that system.

Guardant360 CDx does not make cancer treatment automatic, and it does not guarantee that a targeted drug will work. Its role is more precise: for specific FDA-authorized uses, it can identify molecular features that help determine which patients may be eligible for particular targeted treatments.

That distinction is important.

The real advance is not simply that scientists can detect more mutations. It is that validated molecular information is increasingly being connected directly to approved therapeutic decisions.

As cancer therapies become more biomarker-specific, technologies capable of detecting those biomarkers from a blood sample could become an increasingly important part of the precision-oncology workflow.

5 Most Searched FAQs

1. What is Guardant360 CDx?

Guardant360 CDx is an FDA-authorized blood-based genomic diagnostic that analyzes circulating cell-free DNA to identify specific cancer-related genetic alterations for certain approved treatment-selection uses.

2. Can Guardant360 CDx determine which cancer treatment a patient should receive?

It can help identify patients whose tumors contain specific biomarkers associated with particular FDA-authorized targeted therapies. Treatment decisions still require clinical evaluation by healthcare professionals.

3. Is Guardant360 CDx a biopsy?

It is a liquid biopsy-based test, meaning it analyzes DNA obtained from a blood sample rather than directly removing a piece of tumor tissue. A negative blood result may still require tissue testing when appropriate.

4. Which cancers can Guardant360 CDx help analyze?

FDA-authorized uses include specific treatment-selection applications in cancers such as non-small cell lung cancer, breast cancer and colorectal cancer, depending on the biomarker and therapy involved.

5. Does finding a cancer mutation guarantee that a targeted treatment will work?

No. A biomarker can indicate eligibility for a particular therapy under its approved indication, but it does not guarantee treatment response. Doctors consider the genomic result together with the patient’s cancer and overall clinical situation.