Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
August 05, 2019
2 min read

Liquid biopsy shows efficacy for detection of microsatellite instability

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Scott Kopetz

Guardant360 — a liquid biopsy test through which next-generation sequencing is performed on cell-free DNA extracted from a patient’s blood — appeared effective for detection of microsatellite instability status, according to study data published in Clinical Cancer Research.

The test — which produced results similar to those of standard tissue biopsy — may be used to expand access to immunotherapy among patients with advanced cancer, researchers noted.

“Following the tissue-agnostic approval of pembrolizumab for patients with microsatellite instability [MSI]-high tumors, a barrier to improved outcomes for many patients is the awareness and testing of MSI status,” Scott Kopetz, MD, PhD, associate professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “By adding MSI testing into a noninvasive screening panel, clinicians can routinely scan for this prognostic factor without ordering a separate test.”

MSI is a guideline-recommended biomarker that can help predict response to immunotherapy for patients with solid cancers. However, it is not usually screened for because of tissue insufficiency, unavailability or infeasibility.

Kopetz and colleagues identified 90 microsatellite loci to include in the 74-gene Guardant360 (Guardant Health) panel and validated the test by comparing MSI status results with those of standard-of-care tissue biopsy among 1,145 patients with 40 types of cancer.

Among 949 eligible patients, Guardant360 accurately identified 71 of 82 samples (87%; 95% CI, 77-93) from patients who previously reported as MSI-high, and 863 of 867 samples (99.5%; 95% CI, 98.7-99.8) from patients who reported as MSI-low or MSI-stable.

Researchers also evaluated MSI status by applying the liquid biopsy test to 28,459 clinical plasma samples from patients with advanced cancers. Among this group, Guardant360 identified 278 samples spanning 16 different tumor types as MSI-high.

To validate the test in a clinical setting, researchers presented outcomes for 16 patients with MSI-high metastatic gastric cancer treated with pembrolizumab (Keytruda, Merck; n = 15) or nivolumab (Opdivo, Bristol-Myers Squibb; n = 1) after standard-of-care chemotherapy.

Median duration of treatment was 39 weeks.

Results showed that 10 patients achieved a complete response (n = 7) or partial response (n = 3). An additional three patients had stable disease.

The overall response rate of 63% (95% CI, 36-84) and disease control rate of 81% (95% CI, 95% CI, 54-95) appeared similar to those reported for MSI-high patients determined by standard tissue testing.


Only a subset of the 28,459 plasma samples evaluated for MSI status could be matched with tissue samples, which served as the study’s primary limitation. Further, only one liquid biopsy test was studied, which prohibited application of the results to other tests.

“Our results show that MSI detection in blood samples is not only possible, but valid and informative for immunotherapy selection in patients with a wide range of advanced solid tumors,” researcher Martina Lefterova, MD, PhD, laboratory director and medical director at Guardant Health, said in a press release. “The addition of MSI detection increases the utility of the assay to direct clinicians beyond targeted therapies to include immunotherapies.” – by John DeRosier


Disclosures: The study was funded by Guardant Health. Lefterova reports employment with Guardant Health. Kopetz reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.