A new study, sponsored by AstraZeneca and presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week, suggests that using the Guardant360 CDx test to spot early signs of therapy resistance in advanced breast cancer patients and inform a treatment change could slash the risk of disease progression or death by half.
Guardant Health’s blood test already has one FDA-approved use in breast cancer, as it was greenlit in 2023 as a companion diagnostic for Menarini’s Orserdu. The test, which analyzes circulating tumor DNA (ctDNA), is used to identify patients with ER-positive, HER2-negative advanced or metastatic breast cancer who have ESR1 mutations—which are linked to resistance to standard endocrine therapies—and so may see better results with the oral selective estrogen receptor degrader (SERD).
The Serena-6 study, the results of which were published this month in the New England Journal of Medicine alongside the ASCO presentation, used the test’s ESR1 mutation-spotting abilities to guide treatment changes in breast cancer patients at the earliest signs of resistance to first-line endocrine therapy, even before regular imaging was showing any disease progression.
In the study, more than 3,200 patients with advanced ER-positive, HER2-negative breast cancer were tested with Guardant360 CDx every two or three months. If the test picked up on an emerging ESR1 mutation, and disease progression wasn’t yet showing up in imaging scans, patients were assigned to either continue their endocrine therapy—an aromatase inhibitor plus a CDK4/6 inhibitor—or to swap the aromatase inhibitor for AstraZeneca’s next-gen oral SERD, camizestrant.
Ultimately, 315 patients were eligible for the experiment, with half assigned to each group. An interim analysis of the results found that the patients who switched to camizestrant based on the Guardant test results experienced median progression-free survival of 16 months, compared to 9.2 months for the participants who stayed on endocrine therapy. According to Guardant, that translates to a 56% reduced risk of disease progression or death for the camizestrant group.
Additionally, in an exploratory endpoint for the study, those who switched to camizestrant went a median of 23 months until “a deterioration in the patient-reported global health status and quality of life,” compared to just 6.4 months for those in the endocrine therapy group.
The study is still ongoing, as investigators gather more data to calculate overall survival and time to second disease progression, among other secondary endpoints, per AstraZeneca.
Guardant billed the study as the first such phase 3 trial to rely on a ctDNA-guided approach to spot emerging endocrine resistance and inform a therapy switch before disease progression showed up in imaging, creating “a new paradigm” in cancer treatment, according to Helmy Eltoukhy, Guardant chairman and co-CEO.
“This use of the Guardant360 CDx test highlights how we are pushing the boundaries of what can be done with liquid biopsy in characterizing disease and potential drug efficacy, providing insights that could potentially change clinical practice and improve outcomes in patients with advanced breast cancer,” Eltoukhy added in the company’s announcement Monday.
Outside of breast cancer, the liquid biopsy is also approved as a companion diagnostic to spot several biomarkers in lung cancer patients, to better match them to AstraZeneca’s Tagrisso or Enhertu, Johnson & Johnson’s Rybrevant or Amgen’s Lumakras.