First-Ever Breast Cancer Drug Guided By Blood Tests Before Scans Show Progression Approved By Regulator

The US Food and Drug Administration (FDA) has approved AstraZeneca's breast cancer drug camizestrant. This offers a new treatment option for some people with advanced breast cancer. The drug, which will be sold under the brand name Etcamah, is made for individuals with hormone receptor-positive (HR-positive), HER2-negative locally advanced or metastatic breast cancer whose tumours develop a specific genetic change called an ESR1 mutation while they are receiving hormone therapy and a CDK4/6 inhibitor.

This approval holds significance because the drug can be started when the mutation is detected through a blood test, even before scans show that the cancer has started progressing. Camizestrant is different from many cancer treatments because its use is guided by circulating tumour DNA (ctDNA), which consists of tiny pieces of genetic material released by cancer cells into the bloodstream. The blood test can identify an emerging ESR1 mutation, which may tell that the cancer is becoming resistant to the existing treatment. This eventually allows doctors to consider changing therapy earlier instead of waiting for visible progression on scans.

In the SERENA-6 trial, patients who switched to camizestrant plus a CDK4/6 inhibitor had a median progression-free survival of 16 months, compared with 9.2 months among those who continued their previous treatment.

What Is Camizestrant?

Camizestrant is an oral cancer medicine that belongs to a group called selective estrogen receptor degraders, or SERDs. It works by targeting the estrogen receptor, blocking the hormone's ability to stimulate hormone-sensitive breast cancer cells and helping reduce cancer growth. It is made for cancers that are HR-positive and HER2-negative, which make up a large proportion of breast cancers.

The FDA approval allows camizestrant to be used with one of three CDK4/6 inhibitors: abemaciclib, palbociclib or ribociclib. The recommended dose of camizestrant is 75 mg once daily, with or without food.

Why Is The ESR1 Mutation Important?

ESR1 mutations are one of the ways breast cancer can develop resistance to aromatase inhibitors, which is a commonly used type of hormone therapy. These mutations are uncommon when hormone receptor-positive metastatic breast cancer is first diagnosed but become much more common after treatment with an aromatase inhibitor.

The FDA says that fewer than 5% of patients have the mutation at diagnosis, while nearly 40% may develop it after disease progression on an aromatase inhibitor. This means a patient's tumour can change during treatment. A therapy that was initially controlling the cancer may eventually become less effective. Detecting an ESR1 mutation in the blood can give an early warning that resistance is developing.

How Does The Blood Test Work?

The treatment uses a test that looks for ctDNA in a blood sample. Cancer cells release small amounts of DNA into the bloodstream, and this genetic material can contain mutations linked to treatment resistance.

In the SERENA-6 trial, patients were already receiving an aromatase inhibitor along with a CDK4/6 inhibitor. Blood testing was performed around the time of routine tumour scans. If an ESR1 mutation appeared but scans still showed no disease progression, patients could switch from the aromatase inhibitor to camizestrant while continuing their CDK4/6 inhibitor.

The FDA also approved the Guardant360 CDx test as a companion diagnostic to identify patients with ESR1 mutations who may be eligible for camizestrant.

What Did The Trial Find?

The FDA's approval was based on the Phase III SERENA-6 trial. This included 315 adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer. Participants had detectable ESR1 mutations but no evidence of disease progression when the mutation was found.

The median time before the cancer progressed was 16 months for patients receiving camizestrant with a CDK4/6 inhibitor, compared with 9.2 months for those who continued an aromatase inhibitor with a CDK4/6 inhibitor. However, overall survival data were not mature when the FDA evaluated the primary outcome.

Why Is This Approval Important?

The FDA describes this as the first cancer therapy approved based on detection of a resistance mutation in circulating tumour DNA before imaging tests show that the disease is progressing.

Dr. Angelo de Claro of the FDA's Oncology Center of Excellence, in a news release, said, "This marks the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumour DNA before imaging tests show that the disease is progressing."

However, camizestrant received accelerated approval, meaning additional studies are required to confirm its clinical benefit. The FDA has specifically stated that continued approval may depend on confirmatory evidence.

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