FDA grants Etcamah accelerated approval for ESR1-mutated breast cancer

The FDA granted accelerated approval to AstraZeneca's Etcamah (camizestrant) with a CDK4/6 inhibitor for HR-positive, HER2-negative advanced breast cancer when an ESR1 mutation is detected during aromatase inhibitor therapy. In SERENA-6, median progression-free survival was 16 months versus 9.2 months (HR 0.44); overall survival remained immature on the FDA table.

The FDA granted accelerated approval to AZN's Etcamah (camizestrant) on September 4, allowing an ESR1 mutation detected during breast cancer treatment to trigger a change in endocrine therapy. In the supporting SERENA-6 trial, median progression-free survival was 16 months with camizestrant plus a CDK4/6 inhibitor versus 9.2 months with continued aromatase inhibitor plus CDK4/6 inhibitor therapy. The hazard ratio was 0.44 (95% confidence interval, 0.31–0.60; p<0.00001), according to the FDA.

The accelerated approval covers camizestrant in combination with abemaciclib, palbociclib or ribociclib for adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer upon detection of an ESR1 mutation during aromatase inhibitor plus CDK4/6 inhibitor therapy, based on an FDA-authorized test. The FDA also approved Guardant360 CDx as a companion diagnostic to identify ESR1 mutations for camizestrant treatment.

The treatment decision in SERENA-6 came before radiographic progression. Patients had received first-line aromatase inhibitor plus CDK4/6 inhibitor therapy for at least six months without progression when circulating tumor DNA testing detected an ESR1 mutation. They then either switched the endocrine component to camizestrant, an oral selective estrogen receptor degrader and estrogen receptor antagonist, or continued their aromatase inhibitor, while retaining CDK4/6 inhibition.

The randomized, double-blind, placebo-controlled, multicenter study enrolled 315 patients, assigned 1:1. Its primary endpoint was investigator-assessed progression-free survival under RECIST v1.1. The 95% confidence intervals for median progression-free survival were 12.7–18.2 months in the camizestrant arm and 7.2–9.5 months in the aromatase inhibitor arm. Overall survival was immature at the progression-free survival analysis, the FDA said; the results do not establish that patients live longer.

For patients, the approval creates an option to change treatment when testing identifies emerging ESR1 resistance, before progression on imaging. For investors, it adds an approved use to AZN's oncology portfolio whose uptake will depend in part on how clinicians incorporate circulating tumor DNA monitoring into care. The company described the decision as its tenth FDA approval across its portfolio this year and its fourth in breast cancer. Those counts are company claims.

The FDA said the application received Breakthrough Therapy designation and was reviewed under Project Orbis. The agency also described a standard review timeline for this action.

The safety label is central to that treatment decision. Etcamah carries a boxed warning for the risk of arrhythmia due to QTc prolongation when used with QTc-prolonging drugs. Other warnings include bradycardia and embryo-fetal toxicity. The FDA-recommended dose is 75 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. Patients continue the same CDK4/6 inhibitor dose they were receiving when the ESR1 mutation was detected.

This is accelerated approval, based on progression-free survival measured from mutation detection. Continued approval may require confirmation of clinical benefit. The next questions are whether follow-up establishes confirmatory benefit, including what mature overall survival data show, how widely mutation monitoring is adopted, and how the label's cardiac risks affect treatment decisions.