Camizestrant is the first cancer therapy guided by a ctDNA resistance mutation detected before imaging shows disease progression.
The FDA granted accelerated approval to camizestrant (Etcamah; AstraZeneca) in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor for adult patients with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer whose tumors acquire an ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy. The approval was announced in news releases from the FDA and AstraZeneca.1,2
For pharmacists, the approval introduces a new oral selective estrogen receptor degrader with a boxed warning for arrhythmia risk, meaningful drug-interaction considerations, and a companion diagnostic that changes when the therapy switch happens—before radiographic progression rather than after.1,2
The approval marks the first time the FDA cleared a cancer therapy guided by detection of a resistance mutation in circulating tumor DNA (ctDNA) before imaging shows the disease is progressing, according to Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence. Alongside the drug, the FDA authorized the Guardant360 CDx assay as a companion diagnostic to identify patients with an ESR1 mutation who are candidates for camizestrant.1
ESR1 mutations are the most common mechanism of acquired resistance to aromatase inhibitor-plus-CDK4/6 inhibitor therapy. Fewer than 5% of patients carry the mutation at metastatic diagnosis, but nearly 40% acquire it after progression on an aromatase inhibitor.1,2
Accelerated approval rests on the phase 3 SERENA-6 trial (NCT04964934), presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. In this double-blind study, 3256 patients on first-line aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib [Ibrance; Pfizer], ribociclib [Kisqali; Novartis], or abemaciclib [Verzenio; Eli Lilly]) were monitored for emergent ESR1 mutations in ctDNA every 2 to 3 months. The 315 patients found to have an ESR1 mutation without radiologic progression were randomly assigned 1:1 to switch to camizestrant 75 mg once daily plus their CDK4/6 inhibitor or to continue the aromatase inhibitor plus CDK4/6 inhibitor.1,3,4
Trial Name: Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
ClinicalTrials.gov ID: NCT04964934
Sponsor: AstraZeneca
Estimated Completion Date: September 1, 2028
At a median follow-up of about 12.6 months, median progression-free survival (PFS) was 16.0 months (95% CI, 12.7-18.2) with camizestrant versus 9.2 months (95% CI, 7.2-9.5) with the aromatase inhibitor (hazard ratio [HR], 0.44; 95% CI, 0.31-0.60; P < .0001)—an approximate 56% reduction in the risk of disease progression or death. Median time to deterioration in patient-reported global health status and quality of life was 21.0 months with camizestrant versus 6.4 months with the aromatase inhibitor (HR, 0.54; 95% CI, 0.34-0.84). Because the trial measured PFS from mutation detection rather than confirmed progression, the FDA has required confirmatory studies to verify clinical benefit.1,3
The prescribing information carries a boxed warning: camizestrant with ribociclib—a QTc-prolonging drug and strong CYP3A inhibitor—or with other QTc-prolonging drugs can increase the risk of torsades de pointes, other ventricular arrhythmias, and sudden death. An echocardiogram should be obtained before initiation and monitored during treatment, with electrolyte abnormalities corrected first. In SERENA-6, QTc prolongation occurred in 2.6% of patients and bradycardia in 8%.2,3
Drug-interaction management is central to the pharmacist's role here. Concomitant QTc-prolonging agents (other than ribociclib) and strong CYP3A inducers should be avoided; with a moderate CYP3A inducer, the camizestrant dose increases from 75 mg to 150 mg once daily when combined with abemaciclib or palbociclib. It is also recommended that camizestrant be avoided with CYP2C9 or CYP2C19 substrates.1-3
The most common adverse events (AEs; ≥20% frequency) were largely hematologic—decreased neutrophils (68%), leukocytes (66%), and hemoglobin (47%)—in addition to visual disturbances (34%) and fatigue (23%). The drug also carries a warning for embryo-fetal toxicity, and patients of reproductive potential should use effective nonhormonal contraception. Permanent discontinuation due to AEs was low at approximately 1.3%.2
