‘An Opportunity To Stay One Step Ahead’: FDA Approves Camizestrant at First Sign of Treatment Resistance For Many With Advanced Breast Cancer

The approval does not apply to everyone with this type of advanced breast cancer, though. It specifically applies to those who develop something known as an ESR1 mutation while undergoing treatment with an aromatase inhibitor (a common front-line or first treatment). These mutations help the cancer resist treatment.

“This approval gives us an opportunity to stay one step ahead of the cancer,” Dr. Jaime Alberty, Director of the Comprehensive Breast Center at NYC Health + Hospitals/Kings County, tells SurvivorNet. “For appropriate patients with advanced hormone receptor-positive breast cancer, a blood test can identify an ESR1 mutation, signaling emerging resistance to treatment, allowing us to adjust therapy before the cancer actually progresses on imaging.”

In the press release announcing the approval, acting FDA Commissioner Kyle Diamantas described it as a “win” for patients whose tumors continuously evolve to escape treatment. It gives them access to “a targeted therapy designed specifically to overcome resistance, giving them more time before their disease progresses.”

Who Can Benefit From The Approval?

The approval covers adults with hormone receptor-positive, HER2-negative breast cancer that is locally advanced or metastatic.

• Hormone receptor-positive, often shortened to HR+, means that hormones such as estrogen help the cancer grow.
• HER2-negative means the cancer is not driven by unusually high levels of the HER2 protein.
• Locally advanced cancer has grown extensively in or near the breast, while metastatic cancer has spread to another part of the body.

“This new drug is approved for adults with a specific type of breast cancer (HR-positive, HER2-negative, locally advanced or metastatic) if they have an ESR1 mutation while they’re already on an aromatase inhibitor and a CDK4/6 inhibitor,” Dr. Francisco Esteva, Chief of Hematology & Medical Oncology at Northwell’s Lenox Hill Hospital, tells SurvivorNet.

Patients must already be receiving an aromatase inhibitor, such as anastrozole or letrozole, together with a CDK4/6 inhibitor (abemaciclib, palbociclib or ribociclib). Aromatase inhibitors reduce the amount of estrogen available to stimulate the cancer. CDK4/6 inhibitors slow proteins that cancer cells use to divide.

“The studies looked at patients who had been on that first-line combination for at least six months without their cancer getting worse. So, a patient’s treatment history definitely matters when deciding if this option is right for them,” Dr. Esteva adds.

This is not a treatment started at the initial diagnosis of advanced breast cancer, but one that can be used when a blood test detects an ESR1 mutation developing during the current treatment.

Why Does an ESR1 Mutation Matter?

The ESR1 gene provides instructions for making the estrogen receptor, the part of a cancer cell that receives estrogen’s growth signal. During treatment with an aromatase inhibitor, some cancer cells acquire changes in this gene. The altered receptor may remain active even when estrogen levels are low, allowing the cancer to escape the treatment’s control.

An ESR1 mutation may appear in the blood months before cancer growth becomes visible on a scan. The FDA approved Guardant360 CDx as the companion blood test for identifying patients eligible for this treatment. The blood test looks for circulating tumor DNA, meaning small fragments of DNA released by cancer cells into the bloodstream.

“The biggest change [related to the approval] is ‘when’ doctors can step in,” Dr. Esteva explains. “Other drugs that target this same gene change, like elacestrant and imlunestrant, are usually given after the cancer has already progressed despite previous hormone therapy. Camizestrant offers a chance to change treatment much earlier.”

Camizestrant is an oral estrogen-receptor blocker and degrader. In practical terms, it attaches to the estrogen receptor, blocks its activity, and helps the cell break it down, including receptors altered by ESR1 mutations.

When an eligible mutation is detected, the aromatase inhibitor is replaced with camizestrant. The patient generally continues the same CDK4/6 inhibitor at the same dose. Camizestrant is taken as a 75-milligram tablet once daily, with or without food.

Breaking Down the Data

The approval was based on results from the phase 3 SERENA-6 trial, which included 315 patients whose cancer developed an ESR1 mutation while they were receiving their first treatment with an aromatase inhibitor and a CDK4/6 inhibitor. They had been on that combination for at least six months, and their cancer had not yet worsened on imaging.

Half of the participants switched from the aromatase inhibitor to camizestrant while continuing the CDK4/6 inhibitor. The other half continued their existing combination.

Results were promising:

• Median progression-free survival, the length of time before the cancer worsened or a patient died, was 16 months after the mutation was detection in the camizestrant group, compared with 9.2 months in the group that continued the aromatase inhibitor.
• At 12 months, approximately 61% of patients receiving camizestrant had not had progression, compared with 33% continuing the aromatase inhibitor.
• At 24 months, the figures were approximately 30% and 5%, respectively.
• Overall, the risk of progression or death during follow-up was 56% lower with the camizestrant strategy.

With longer follow-up, the time until a second episode of progression, after patients received another treatment, was also longer: 25.7 months versus 19.1 months.

However, the study has not shown that switching early helps patients live longer overall. The current overall-survival results remain uncertain and could still be consistent with benefit, no meaningful difference, or harm.

Another unanswered question is whether switching immediately is better than detecting the mutation, continuing the current treatment until scans show progression and then changing therapy. SERENA-6 did not directly compare those two strategies. This is why the FDA used its accelerated-approval pathway and is requiring additional studies to confirm the clinical benefit.

Treatment & Monitoring: What to Expect

Dr. Sonya Reid, an associate professor of medicine in the Division of Hematology/Oncology at Vanderbilt-Ingram Cancer Center, calls the approval “paradigm-shifting,” and notes that regular liquid biopsies will be necessary to monitor patients on first-line therapy.

“This approval supports a more proactive approach by using a blood test to detect emerging resistance to endocrine therapy. Patients will then have the option to potentially switch to camizestrant earlier, rather than waiting for progression on scans,” Dr. Reid tells SurvivorNet.

“This is, however, not a one-size-fits-all decision. Patients should have a shared discussion with their medical oncology team, taking into account how well first-line treatment is being tolerated, current symptoms, and imaging results,” she adds.

Because patients continue their CDK4/6 inhibitor even after switching to camizestrant, familiar effects such as low white blood cell counts, anemia, fatigue, or diarrhea may continue. Blood tests remain important.

Camizestrant itself can cause visual symptoms, including brief flashes of light, blurred vision, double vision or sensitivity to light. In the trial, these effects were generally mild, but new or worsening visual symptoms should be reported.

Heart monitoring is particularly important. Camizestrant can slow the heart rate and, in combination with certain medications, alter the heart’s electrical rhythm. Its prescribing information carries a boxed warning about potentially serious abnormal rhythms when it is taken with medications that also affect this electrical timing.

The treatment was rarely stopped because of side effects in SERENA-6, but trial participants were generally well enough to carry out normal daily activities and the study did not include people with certain pre-existing heart risks.

Questions To Ask Your Doctor

• How often will I need blood tests or scans while undergoing breast cancer treatment?
• Should I have regular circulating tumor DNA testing for ESR1 mutations?
• If an ESR1 mutation is found before my scans change, what are the benefits and risks of switching to camizestrant?
• Would I continue my current CDK4/6 inhibitor and dose, or are there reasons to change it?
• What side effects should I monitor for with the camizestrant + CDK4/6 combination?

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