FDA Approves Camizestrant for Early ESR1-Mutant Breast
The FDA granted accelerated approval to camizestrant for HR+/HER2- breast cancer when ESR1 resistance mutations are first detected during initial therapy.
The U.S. Food and Drug Administration has approved a new drug for a specific, early-stage change in advanced breast cancer. Camizestrant (Etcamah) received accelerated approval on Friday for treating hormone receptor-positive, HER2-negative breast cancer at the first detection of ESR1 resistance mutations during first-line treatment. It is an oral selective estrogen receptor degrader (SERD) to be used with a CDK4/6 inhibitor when these mutations are found via blood test during combination therapy with an aromatase inhibitor and a CDK4/6 inhibitor.
This marks a novel approach. It is the first approval in cancer where treatment is switched not because of radiographic progression seen on scans, but because resistance mutations are detected by circulating tumor DNA in the blood. The FDA's decision was made contrary to the recommendations of its outside expert advisors.
The agency acknowledged the uncertainty. "Since it is not yet confirmed whether intervening at this point, rather than at the time of confirmed disease progression, translates into a clinically meaningful benefit, the FDA has required confirmatory studies to verify and describe clinical benefit," it stated.
SERENA-6 Trial Results
The approval was based on the phase III SERENA-6 trial. The study involved patients who were responding to an aromatase inhibitor and a CDK4/6 inhibitor. When an ESR1 mutation was detected via blood test, researchers switched the aromatase inhibitor for camizestrant while continuing the CDK4/6 inhibitor. This switch reduced the risk of disease progression or death by 56%.
Median progression-free survival improved substantially. It increased from 9.2 months for patients who stayed on the aromatase inhibitor to 16 months for those who switched to camizestrant.
Investigator Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, highlighted the impact. "The combination provides an important new option for the one in three patients with this form of advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression," he said in an AstraZeneca press release. He added that the approval lets clinicians change strategy earlier, before the cancer becomes harder to treat and patient quality of life worsens.
Advisory Committee Concerns
Despite the progression-free survival benefit, the FDA's Oncologic Drugs Advisory Committee had reservations. At a meeting in April, most panelists said the trial did not clearly establish a clinically meaningful benefit for patients who switched therapy solely based on the ESR1 mutation detection. Overall survival data from the trial were immature at the time of analysis.
Safety Profile and Warnings
The drug combination carries a notable side effect profile. Common adverse events occurring in 20% or more of patients included visual disturbances, fatigue, and decreases in various blood cell counts.
The prescribing information includes a boxed warning for the risk of arrhythmia due to QTc interval prolongation, particularly when camizestrant is used with other drugs that prolong the QTc interval, such as the CDK4/6 inhibitor ribociclib (Kisqali). It also carries warnings for bradycardia and embryo-fetal toxicity.
Companion Diagnostic Approved
Alongside the drug, the FDA approved the Guardant360 CDx assay. This blood test is a companion diagnostic device to identify patients with ESR1 mutations who are eligible for treatment with camizestrant.
