Camizestrant led to a statistically significant improvement in progression-free survival compared to fulvestrant in postmenopausal patients with metastatic, locally advanced, or estrogen receptor-positive breast cancer who had previously been treated with endocrine therapy for advanced disease.
Camizestrant (AZD9833) led to a statistically significant and clinically significant improvement in progression-free survival (PFS) compared to fulvestrant (Faslodex) in postmenopausal patients with estrogen receptor (ER)-positive, locally advanced or metastatic breast cancer who received prior treatment with endocrine therapy for advanced disease, based on key findings from the phase 2 SERENA-II trial (NCT04214288).1
Camizestrant was well tolerated and its safety profile was similar to that reported in previous trials with no new safety signals. The data will be presented at an upcoming medical meeting.
“The SERENA-2 results show that camizestrant provides a significant improvement in PFS compared to fulvestrant, which has been used to treat patients with [hormone receptor] HR positive breast cancer for almost twenty years. These results are significant and highlight the potential of this new oral generation [selective estrogen receptor degrader] SERD and supporting the ongoing research program,” said Mafalda Oliveira, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, Spain and principal investigator on the phase 2 SERENA-2 trial, in a press release. press.
Endocrine therapies are commonly used to treat patients with HR-positive breast cancer, but many patients with advanced disease will develop resistance to CDK4/6 inhibitors and ER-targeted therapies in the front-line setting, creating a need of effective second-line treatment. .
Camizestrant is a potent, next-generation oral SERD and pure ERα antagonist, which has demonstrated antitumor activity in a variety of preclinical models, including those with activating ER mutations.
SERENA-2 is a randomized, open-label, multicenter Phase 2 trial evaluating camizestrant at various dose levels compared to fulvestrant in ER-positive, HER2-negative advanced breast cancer.
To be eligible for enrollment, patients must be at least 18 years of age and have documented radiological or other objective evidence of progression on or after their last systemic therapy; at least 1 lesion, not previously irradiated, that can be accurately measured at baseline as at least 10 mm in longest diameter, or at least 1 lytic or mixed bone lesion; and an ECOG performance status of 0 or 1.two
Co-primary endpoints are PFS defined by RECIST v1.1 criteria comparing camizestran 75 mg with fulvestrant 500 mg and camizestran 150 mg with fulvestrant. Secondary endpoints include safety, objective response rate, and clinical benefit rate at 24 weeks.
A total of 240 patients were randomly assigned to receive camizestrant or fulvestrant until disease progression.
“Our goal with our next-generation oral SERD camizestrant is to improve currently available endocrine therapies for patients with HR-positive breast cancer in early and metastatic disease. The exciting efficacy and compelling safety results from the SERENA-2 trial underscore the potential for camizestrant to achieve this goal in patients with ER-driven breast cancer and we look forward to advancing our comprehensive Phase 3 clinical program for camizestrant,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca.
Camizestrant is being studied in multiple trials in advanced breast cancer, including the pivotal Phase 3 SERENA-6 trial (NCT04964934) evaluating camizestran in combination with the CDK4/6 inhibitors palbociclib (Ibrance) and abemaciclib (Verzenio) in patients with HR positive metastatic cancer. breast cancer that has detectable ESR1 mutations in first-line treatment, and the phase 3 SERENA-4 trial (NCT04711252) evaluating camizestrant plus palbociclib as first-line treatment in patients with HR-positive, locally advanced or metastatic breast cancer.
The indication for SERENA-6 received fast track designation from the FDA.
- Camizestrant significantly improved progression-free survival versus faslodex in the phase II SERENA-2 trial in advanced ER-positive breast cancer. Press release. AstraZeneca. October 26, 2022. Retrieved October 26, 2022. https://bit.ly/3N8lvMg
- A comparative study of AZD9833 versus fulvestrant in women with advanced ER-positive HER2-negative breast cancer (SERENA-2). ClinicalTrials.gov. Updated October 20, 2022. Retrieved October 26, 2022. https://clinicaltrials.gov/ct2/show/NCT04214288