FDA Approves Guardant360 Test With Inluriyo for ESR1 Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved its Guardant360® CDx as a companion diagnostic to identify patients with advanced breast cancer that exhibit ESR1 mutations who may benefit from Inluriyo (imlunestrant), according to a news release from Guardant.

Guardant360 CDx, a blood test, was approved alongside Inluriyo to help treat adults with advanced or metastatic breast cancer that has an ESR1 mutation and whose disease got worse after at least one prior hormone therapy.

“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,” Helmy Eltoukhy, Guardant health chairman and co-CEO, said in the news 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.”

In the phase 3 EMBER-3 trial, Guardant360 CDx was used to find patients with ESR1 mutations. Results showed that patients treated with Inluriyo had a 38% lower risk of disease progression or death compared with hormone therapy. Patients with certain ESR1 mutations, including E380, V422del, S463, L469, L536, Y537 and D538, may be eligible for treatment with Inluriyo.

The FDA approval of Inluriyo alongside Guardant360 CDx marks the sixth approved use of this test and the second in breast cancer, following an earlier approval with Orserdu in 2023, as per the release.

Guardant360 CDx was the first FDA-approved blood test for comprehensive genomic testing. It is currently approved to guide treatment decisions in multiple cancers, including non-small cell lung cancer and breast cancer with ESR1 mutations. The test is widely covered by Medicare and private insurers, making it accessible to more than 300 million people.

Inluriyo FDA Approval for ER-positive, HER2-negative, ESR1-mutated metastatic Breast Cancer

The FDA recently approved Inluriyo (imlunestrant, 200 milligram tablets) for adults with estrogen receptor-positive, HER2-negative breast cancer.

The oral estrogen receptor antagonist is indicated for patients whose disease carries an ESR1 mutation and has advanced or metastasized. It is also meant for those whose cancer worsened after at least one prior endocrine therapy.

Approval was supported by results from the EMBER-3 trial, which enrolled 256 patients with ESR1-mutated metastatic breast cancer. Participants received either Inluriyo or endocrine therapy. Some were treated in the first-line setting after recurrence following adjuvant aromatase inhibitor therapy, with or without prior CDK4/6 inhibition (21%), while others received second-line treatment after disease progression on aromatase inhibitors, with or without prior CDK4/6 inhibition (79%).

Findings showed that Inluriyo reduced the risk of disease progression or death by 38% compared with standard endocrine therapy. Median progression-free survival was 5.5 months for patients treated with Inluriyo versus 3.8 months with Faslodex (fulvestrant) or Aromasin (exemestane).

What are the Side Effects of Inluriyo?

In the EMBER-3 trial, most side effects from Inluriyo were classified as mild to moderate. The most frequent side effects, reported in 10% or more of patients and including laboratory changes, were low hemoglobin, muscle or joint pain, low calcium, low neutrophils, elevated liver enzymes (AST and ALT), fatigue, diarrhea, higher triglycerides, nausea, low platelets, constipation, increased cholesterol and abdominal pain.

Overall, 4.6% of patients discontinued treatment permanently because of side effects, while 2.4% required dose reductions and 10% experienced treatment interruptions.

Reference

1. “U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer.” Eli Lilly and Company. News Release. Sep 25, 2025.
2. “FDA Approves Inluriyo for ER+, HER2– Metastatic Breast Cancer.” CURE Media Group. Sep 25. 2025.

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