FDA Approves Guardant 360 CDx With Imlunestrant in ESR1+ Breast Cancer

The FDA has approved the Guardant 360 CDx as a companion diagnostic to identify ESR1 mutation in patients with advanced breast cancer who may benefit from treatment with imlunestrant (Inluriyo).¹

On September 25, the FDA approved imlunestrant for the treatment of adult patients with estrogen receptor (ER)-positive, HER2–, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed after at least 1 line of endocrine therapy.²

“This FDA approval provides another treatment for breast cancer patients with ESR1 mutations for their specific type of cancer along with expanded access to comprehensive genomic profiling with a simple blood draw,” said Helmy Eltoukhy, Guardant Health chairman and co-CEO, in a press release. “Precision testing plays a critical role in helping physicians identify the correct treatment, providing patients and their doctors with the comprehensive genomic profiling needed to see if they are eligible to receive the right treatment and improving outcomes.”

Guardant 360 CDx was used in the phase 3 EMBER-3 trial (NCT04975308) that led to the approval of imlunestrant. In the trial, imlunestrant reduced the risk of disease progression or death by 38% vs endocrine therapy.³ Results demonstrated that patients with ESR1-mutated disease treated with imlunestrant monotherapy (n = 138) experienced a median progression-free survival (PFS) of 5.5 months (95% CI, 3.9–7.4) vs 3.8 months (95% CI, 3.7–5.5) for those given standard-of-care endocrine therapy of fulvestrant or exemestane (n = 118; HR, 0.62; 95% CI, 0.46-0.82; P <.001).

In the overall population, the median PFS was 5.6 months (95% CI, 5.3–7.3) with imlunestrant monotherapy (n = 331) compared with 5.5 months (95% CI, 4.6–5.6) for endocrine therapy (n = 330; HR, 0.87; 95% CI, 0.72–1.04; P =.12). Notably, there was no statistical difference in PFS between the 2 arms for patients without ESR1 mutations (HR, 1.00; 95% CI, 0.79–1.27).

In patients with measurable disease in the overall population, the investigator-assessed overall response rate (ORR) was 12% (95% CI, 8%–16%) with imlunestrant (n = 262) vs 8% (95% CI, 5%–12%) with endocrine therapy (n = 251). The ORR was 14% (95% CI, 8%–21%) for imlunestrant alone (n = 112) vs 8% (95% CI, 2%–13%) for endocrine therapy (n = 91) in the ESR1-mutated population; the respective ORRs were 11% (95% CI, 6%–16%) and 9% (95% CI, 4%–13%) for imlunestrant (n = 150) and endocrine therapy (n = 160) in the population without ESR1 mutations.

Safety data showed that any-grade treatment-emergent adverse events (TEAEs) were observed in 83% of patients in the imlunestrant monotherapy arm (n = 327) vs 84% of patients in the endocrine therapy arm (n = 334). The rates of grade 3 or higher TEAEs were 17% and 21%, respectively. The most common any-grade TEAEs reported in at least 10% of patients included fatigue (imlunestrant, 23%; endocrine therapy, 13%), diarrhea (21%; 12%), nausea (17%; 13%), arthralgia (14%; 14%), increased aspartate aminotransferase levels (13%; 13%), back pain (11%; 7%), increased alanine aminotransferase levels (10%; 10%), anemia (10%; 13%), and constipation (10%; 6%).

Serious AEs were reported in 10% of patients in the imlunestrant arm vs 12% of patients in the endocrine therapy arm. In the imlunestrant monotherapy arm, AEs led to dose reductions, treatment discontinuation, and death in 2%, 4%, and 2% of patients, respectively. These respective rates were 0%, 1%, and 1% in the endocrine therapy group.

REFERENCES:

1. FDA Approves Guardant360® CDx as Companion Diagnostic for Eli Lilly and Company’s Inluriyo™ (imlunestrant) for Treatment of ESR1-mutated Advanced Breast Cancer. News release. Guardant Health, Inc. September 29, 2025. Accessed September 29, 2025. https://tinyurl.com/4tx38zwz

2. FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. US FDA. News release. September 25, 2025. Accessed September 29, 2025. https://tinyurl.com/3p5axp5n

3. Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): results of the phase 3 EMBER-3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; Abstract GS1-01.