FDA Okays Guardant360 Test as CDx for Elacestrant in ESR1-mutated Breast Cancer


The Guardant360 CDx, which will identify patients with advanced or metastatic breast cancer who have ESR1 mutations and may benefit from elacestrant, is the fifth test to be approved by the FDA and first for patients with breast cancer.

The FDA has approved the Guardant360 CDx liquid biopsy test as a companion diagnostic for patients with advanced or metastatic breast cancer harboring ESR1 mutations who may derive benefit from treatment with elacestrant (Orserdu).1

Guardant360 CDx is a blood test which delivers comprehensive genomic profiling to aid in identifying patients who harbor ESR1 mutations. The test will be used as a companion diagnostic for those who may benefit from elacestrant as a targeted therapy, which is a nonsteroidal selective estrogen receptor degrader (SERD).2

The approval as a companion diagnostic for elacestrant is Guardant Health’s fifth FDA approval for the Guardant360 CDx test and its first for patients with breast cancer.

"This exciting news represents the approval of the first novel, oral SERD, and elacestrant will be an important new therapeutic option for patients with metastatic HR-positve breast cancer. This development also represents another major step forward in the field of precision oncology, as results from the EMERALD study suggested that patients with ESR1 mutations had the potential to demonstrate more benefit from elacestrant use after prior progression on hormonal and CDK4/6 inhibitor therapy. The presence or absence of an ESR1 mutation, like PIK3CA mutations, will be a key factor on treatment planning for physicians and patients, will further allow personalization of drug selection as we strive to improve care for metastatic breast cancer," Seth Wander, MD, PhD, Massachusetts General Hospital, told Targeted OncologyTM.

“This FDA approval is great news for [patients with] breast cancer with ESR1 mutations, who now have, for the first time, an approved treatment for their specific type of cancer and a blood-based companion diagnostic,” said Helmy Eltoukhy, Guardant Health co-chief executive officer. “We are pleased that the Guardant360 CDx liquid biopsy is now approved so that oncologists and their patients can access comprehensive genomic profiling to see if they are eligible to receive this therapy.”

In women, breast cancer is the second leading cause of death related to cancer and according to The American Cancer Society, about 297,790 new cases of invasive breast cancer will be diagnosed in women in 2023.

Elacestrant was recently approved by the FDA in January, 2023. It is the first therapy to be granted approval by the FDA for advanced breast cancer patients with ESR1 mutations who have had disease progression following at least 1 line of endocrine therapy.

Approval was based on data from the phase 3 EMERALD trial (NCT03778931) where treatment with elacestrant met the studies co-primary end points of progression-free survival (PFS) in all patients.3

Findings showed that at a median follow-up of 15.5 months, elacestrant reduced the risk of progression or death by 30% (HR, 0.70; 95% CI, 0.55-0.88; P = .0018) in all patients. The median PFS was 2.8 months for elacestrant vs 1.9 months with SOC.3 For patients with a confirmed ESR1 mutation (47.8%), treatment with elacestrant reduced the risk of progression by 45% (HR, 0.55; 95% CI, 0.39-0.77; P = .0005).

"It is important to recognize that ESR1 mutations are relatively rare in untreated HR-positive breast cancer, and typically develop under selective pressure on hormonal therapy. Clinicians should consider testing or retesting for ESR1 mutations after progression on hormonal and CDK4/6 inhibitor therapy given the increasingly prevalence of these mutations in this patient group. Elacestrant was generally well-tolerated in the EMERALD study, with side effects including hot flashes, nausea, fatigue, and some laboratory abnormalities noted," added Wander.

In addition to this approval for Guardant360 CDx as a companion diagnostic to elacestrant for patients with advanced breast cancer and ESR1 mutations, the agent is also approved to identify patients with non–small cell lung cancer who may benefit from treatment with osimertinib (Tagrisso), amivantamab-vmjw (Rybrevant), fam-trastuzumab deruxtecan-nxki (Enhertu) or sotorasib (Lumakras).

“We are proud to bring the very first treatment targeting ESR1 mutations which are present in up to 40% of ER+/HER2- advanced breast cancers,” commented Elcin Barker Ergun, chief executive officer of Menarini Group, in the press release. “We’re also pleased with the approval of the Guardant360 CDx blood test as the companion diagnostic to help oncologists identify patients who may benefit from this innovative endocrine therapy.”

1. Guardant Health receives FDA approval for Guardant360® CDx as companion diagnostic for Menarini Group’s ORSERDU™ for treatment of patients with ESR1 mutations in ER+, HER2- advanced or metastatic breast cancer. News Release. Guardant Health, Inc. January 30, 2023. Accessed January 30, 2023. https://bit.ly/3HGF5hu
2. Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. doi:10.1186/s13058-021-01462-3
3. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338
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