Camizestrant, a next-generation selective estrogen receptor degrader, outperformed fulvestrant in a phase 2 trial, according to a presentation at the San Antonio Breast Cancer Symposium 2022.
Camizestrant improved progression-free survival (PFS) in postmenopausal patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer who had recurrence or progression with at least 1 prior line of endocrine therapy.
The phase 2 trial, SERENA-2 (ClinicalTrials.gov Identifier: NCT04214288), included 240 patients with a median age of 60.0 (range, 35-89) years at baseline. A majority of patients (58.3%) had lung or liver metastasis, 36.7% had detectable ESR1 mutations, 66.7% had received endocrine therapy, and 49.6% had received CDK4/6 inhibitors.
The patients were randomly assigned to receive fulvestrant at 500 mg (n=73) or camizestrant at 1 of 3 doses — 75 mg (n=74), 150 mg (n=73), or 300 mg (n=20). However, the 300 mg treatment arm was terminated early for non-toxicity-related reasons, and the arm was not included in this analysis.
The primary endpoint was PFS. The median PFS was 7.2 months with the 75 mg dose of camizestrant, 7.7 months with the 150 mg dose of camizestrant, and 3.7 months with fulvestrant.
PFS was significantly improved with camizestrant at the 75 mg dose (adjusted hazard ratio [aHR], 0.58; 90% CI, 0.41-0.81; P =.0124) and at the 150 mg dose (aHR, 0.67; 90% CI, 0.48-0.92; P =.0161), compared with fulvestrant.
Both doses of camizestrant were associated with improved PFS in subgroups of patients with unmet needs, including those with detectable ESR1 mutations at baseline, patients who had prior CDK4/6 inhibitor treatment, patients with lung or liver metastasis, and patients with ER-driven disease.
In patients with ESR1 mutations, camizestrant treatment was associated with a reduction in ESR1-mutant circulating tumor DNA (ctDNA) to undetectable or near undetectable levels by cycle 2, which was maintained through cycle 7. Fulvestrant was also associated with a reduction in ESR1-mutant ctDNA but not to the same extent.
Treatment-emergent adverse events (AEs) occurred in 77.0% of patients who received low-dose camizestrant, 90.4% of those who received high-dose camizestrant, and 68.5% of those who received fulvestrant. AEs leading to dose reduction occurred in 1.4%, 12.3%, and 0%, respectively. AEs leading to dose interruptions occurred in 14.9%, 21.9%, and 4.1%, respectively.
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next-generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. Presented at SABCS 2022. December 6-10, 2022. Abstract GS3-02.