FDA Approves Guardant360 CDx Liquid Biopsy for Genomic Profiling for Solid Cancers


The FDA has approved Guardant360® CDx for comprehensive genomic profiling in patients with any solid malignant cancer.

The FDA has approved Guardant360® CDx for comprehensive genomic profiling in patients with any solid malignant cancer, according to an announcement from Guardant Health, Inc.1 The assay is also approved as a companion diagnostic to detect EGFR mutations in patients with non­—small cell lung cancer (NSCLC) who could potentially benefit from osimertinib (Tagrisso).

The regulatory decision was based on both clinical and analytical data from over 5,000 samples, which provided validation for the test.

“The FDA approval of Guardant CDx is a landmark decision, demonstrating the value liquid biopsy delivers to oncologists and more importantly, the patients they treat. Traditional tissue biopsy-based tumor profiling, which is often invasive and has longer turnaround times, can contribute to delays in starting treatment and possibly suboptimal therapy,” Helmy Eltoukhy, CEO of Guardant Health, stated in a press release.

“We applaud the FDA for their collaborative review process and for approving the first comprehensive genomic profiling liquid biopsy test,” added Eltouky. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx.”

Results from a retrospective analysis of findings from the phase 3 FLAURA and AURA3 trials showed that patients who had been identified for osimertinib treatment by the Guardant360 CDx test experienced progression-free survival (PFS) rates that proved to be consistent with those identified through the use of traditional biomarker testing, according to Guardant Health.

Data from the phase 3 FLAURA trial indicated that treatment with osimertinib led to a significant overall survival compared with erlotinib (Tarceva) or gefitinib (Iressa) in patients with EGFR-mutated locally advanced or metastatic NSCLC.2 Previously reported PFS data from the trial led to the April 2018 FDA Approval of the agent for use in this setting.

Data from the trial demonstrated that osimertinib led to a 54% reduction in the risk of progression or death compared with erlotinib or gefitinib. The median PFS with osimertinib was 18.9 months with osimertinib versus 10.2 months with standard treatment (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).3

A total of 556 patients with treatment-naïve EGFR-mutated locally advanced or metastatic NSCLC were enrolled on the trial. These participants were randomized to receive either osimertinib (n = 279) or erlotinib or gefitinib (n = 277). Notably, participants with central nervous system (CNS) metastases were permitted to participate. All included had exon 19 deletions or L858R mutations. Patients received oral osimertinib at 80 mg daily, or 250 mg of gefitinib or 150 mg of erlotinib daily.

Notably, the PFS benefit was found to be upheld across all of the patient subgroups analyzed. In the 116 patients with CNS metastases, the median PFS with osimertinib versus a standard TKI was 15.2 months and 9.6 months, respectively (HR, 0.47; 95% CI, 0.30-0.74; P = .0009). In the 440 participants who did not have CNS involvement, the median PFS was 19.1 months in the osimertinib arm compared with 10.9 months in the standard arm (HR, 0.46; 95% CI, 0.36-0.59; P <.0001).

Moreover, the objective response rates (ORRs) were 77% versus 69% with osimertinib and standard treatment, respectively, and the median duration of response was 17.6 months and 9.6 months, respectively.

With regard to safety, the most commonly reported toxicities with osimertinib included diarrhea (58%) and dry skin (32%); in the control group, the most common all-grade adverse effects (AEs) were diarrhea (57%) and dermatitis acneiform (48%). Grade 3 or higher effects were reported in 33.7% of patients in the investigational arm versus 44.8% of those in the control arm. Notably, those who received treatment with osimertinib were less likely to discontinue treatment because of toxicities compared with those who receive standard TKI treatment, at 13.3% versus 18.1%, respectively.

In March 2017, the FDA has granted a regular approval to osimertinib for use in patients with EGFR T790M mutation—positive NSCLC post treatment with an EGFR TKI, based on PFS data from the pivotal phase 3 AURA3 trial.4

In this trial, treatment with osimertinib resulted in a median PFS of 10.1 months versus just 4.4 months with platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.001). In those with CNS metastases, the median PFS with osimertinib was 8.5 months versus 4.2 months with chemotherapy (HR, 0.32; 95% CI, 0.21-0.49).

In the open-label trial, a total of 419 patients were randomly assigned 2:1 to receive either osimertinib (n = 279) versus a platinum-based chemotherapy regimen (n = 140). Oral osimertinib was given at 80 mg once daily in a 21-day treatment cycle. Those in the chemotherapy arm received either pemetrexed/carboplatin or pemetrexed/cisplatin. Pemetrexed was given at 500 mg/m2, carboplatin at a dose of 5 AU, and cisplatin at 75 mg/m2.

Results showed that osimertinib led to a 71% ORR compared with 31% in those who received chemotherapy (odds ratio, 5.39; 95% CI, 3.47-8.48; P <.001). Moreover, osimertinib showed a 6-month PFS rate of 69% versus 37% with chemotherapy. The 12-month PFS rates were 44% and 10% in the osimertinib and chemotherapy arms, respectively.

Regarding safety, the most common toxicities reported with osimertinib were diarrhea (41%), rash (34%), dry skin (23%), and paronychia (22%). In patients who received the chemotherapy, the most common all-grade AEs included nausea (49%), decreased appetite (36%), constipation (35), and fatigue (28%).

Grade 3 or higher toxicities occurred in 23% and 47% of those on the osimertinib and chemotherapy arms, respectively. Neutropenia (12%), anemia (12%), and thrombocytopenia (7%), were among the most commonly reported grade 3 or higher AEs experienced in the chemotherapy arm.

“Personalized medicines such as [osimertinib] have been truly life-changing for many [patients with] who have certain EGFR mutations and are most likely to benefit from this medicine,” Jhanelle Gray, MD, senior member and chair in the Department of Thoracic Oncology and co-leader of Chemical Biology & Molecular Medicine Program at Moffitt Cancer Center, added in the release. “It is crucial that all patients are comprehensively tested before starting treatment to ensure they receive the most appropriate personalized treatment option available.”


1. Guardant Health Guardant360® CDx first FDA-approved liquid biopsy for comprehensive tumor mutation profiling across all solid cancers. News release. Guardant Health, Inc. August 7, 2020. Accessed August 7, 2020. https://bit.ly/2C6asTE.

2. Tagrisso significantly improves overall survival in the Phase III FLAURA trial for 1st-line EGFR-mutated non-small cell lung cancer. AstraZeneca. Posted August 9, 2019. Accessed August 9, 2019. https://bit.ly/2ZGF7gZ.

3. Ramalingam S, Reungwetwattana T, Chewaskulyong B, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA. Ann Oncol. 2017;28(suppl 5):v635. doi:10.1093/annonc/mdx440.050

4. Mok TS, Wu YL, Ahn MJ, et al. AURA3 Investigators. Osimertinib or platinum—pemetrexed in EGFR T790M—positive lung cancer. N Engl J Med. 2017;376(7):629-640. doi:10.1056/NEJMoa1612674

This article was originally published on OncLive as, "FDA Approves Guardant360 CDx Liquid Biopsy for Comprehensive Genomic Profiling Across All Solid Cancers."

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