FDA Approves Etcamah Plus CDK4/6 Inhibitor for ESR1-Mutated Breast Cancer

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Etcamah (camizestrant) in combination with a CDK4/6 inhibitor for certain adults with advanced breast cancer.

The treatment is approved for adults with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer whose tumors develop an ESR1 mutation while they are receiving an aromatase inhibitor and a CDK4/6 inhibitor.

The approval expands treatment options for patients whose cancers develop resistance to commonly used hormone therapy.

What are ESR1 mutations?

ESR1 mutations are changes in the estrogen receptor gene that can develop as breast cancer adapts to treatment with an aromatase inhibitor.

These mutations are uncommon when HR-positive metastatic breast cancer is first diagnosed, occurring in fewer than 5% of patients. However, they become much more common after the cancer progresses while a patient is receiving an aromatase inhibitor, with nearly 40% of patients developing an ESR1 mutation.

Because ESR1 mutations can contribute to treatment resistance, identifying them may help doctors determine when a patient's cancer is beginning to adapt to therapy.

A new approach to detecting treatment resistance

One notable aspect of the approval is that treatment can be started when an ESR1 mutation is detected in the blood, before imaging shows that the cancer has progressed.

The mutations can be detected using circulating tumor DNA (ctDNA). ctDNA consists of small pieces of DNA released by cancer cells into the bloodstream.

This means a blood test may identify molecular signs that the cancer is becoming resistant to treatment before changes can be seen on scans.

"This marks the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumor DNA (ctDNA) before imaging tests show that the disease is progressing," said Angelo de Claro, M.D., director of the FDA's Oncology Center of Excellence. "But additional evidence is needed to confirm clinical benefit."

What did the clinical trial show?

The approval was supported by a clinical trial that evaluated switching patients to Etcamah plus a CDK4/6 inhibitor after an ESR1 mutation was detected.

Patients were treated with Etcamah in combination with abemaciclib, palbociclib or ribociclib, or continued treatment with an aromatase inhibitor plus a CDK4/6 inhibitor.

The estimated median progression-free survival was:

• 16 months for patients receiving Etcamah plus a CDK4/6 inhibitor
• 9.2 months for patients who continued an aromatase inhibitor plus a CDK4/6 inhibitor

Progression-free survival refers to the length of time during and after treatment that a patient's cancer does not get worse.

Why is this an accelerated approval?

The FDA's accelerated approval pathway allows certain treatments for serious conditions to reach patients sooner when they address an unmet medical need and show promising results using a surrogate or intermediate measure.

In this case, the approval was based on progression-free survival measured from the time the ESR1 mutation was detected in the blood.

However, it is not yet known whether treating patients at the time an ESR1 mutation is detected — before cancer progression is confirmed on imaging — ultimately provides a meaningful clinical benefit.

Because of this, the FDA requires confirmatory studies to verify the treatment's benefit.

A companion diagnostic can help identify eligible patients

Along with the treatment approval, the FDA authorized the Guardant360 CDx assay as a companion diagnostic.

The test is designed to identify patients with breast cancer whose tumors have ESR1 mutations and who may be eligible for treatment with camizestrant.

What are the potential side effects?

Etcamah's prescribing information includes a boxed warning for the risk of irregular heart rhythm when the treatment is taken with certain other medications.

The prescribing information also includes warnings about:

• Abnormally slow heart rate
• Potential harm to an unborn baby

Patients should talk with their cancer care team about their individual risks, other medications they are taking and whether testing for ESR1 mutations is appropriate for them.

For patients with HR-positive, HER2-negative advanced breast cancer, the approval provides another treatment option when their cancer begins showing signs of resistance to aromatase inhibitor therapy.

References

1. U.S. Food and Drug Administration. “FDA Grants Accelerated Approval to Camizestrant for Advanced Breast Cancer With ESR1 Mutations.” September 4, 2026.