Camizestrant Improves PFS Vs Fulvestrant in Advanced ER+ Breast Cancer

Susan Galbraith

Camizestrant (AZD9833) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with fulvestrant (Faslodex) in postmenopausal patients with estrogen receptor (ER)–positive, locally advanced, or metastatic breast cancer who were previously treated with endocrine therapy for advanced disease, according to topline findings from the phase 2 SERENA-II trial (NCT04214288).¹

Camizestrant was well tolerated, and its safety profile was similar to that reported in prior trials with no new safety signals. The data will be presented at an upcoming medical meeting.

“The results from SERENA-2 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 meaningful, highlighting the potential of this next-generation oral [selective estrogen receptor degrader] SERD and supporting the ongoing research program,” Mafalda Oliveira, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, Spain and lead investigator in the SERENA-2 phase 2 trial, said in a press release.

Endocrine therapies are commonly used for the treatment of patients with HR-positive breast cancer, but many patients with advanced disease will develop resistance to CDK4/6 inhibitors and ER-targeting therapies in the frontline setting, creating a need for effective second-line treatment.

Camizestrant is a potent, next-generation oral SERD and pure ERα antagonist, that has demonstrated antitumor activity across a range of preclinical models, including those with ER-activating mutations.

SERENA-2 is a randomized, open-label, multicenter phase 2 trial evaluating camizestrant at several dose levels compared with fulvestrant in advanced ER-positive, HER2-negative 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 measured accurately at baseline as at least 10 mm in the longest diameter, or at least 1 lytic or mixed bone lesion; and an ECOG performance status of 0 or 1.²

The coprimary end points are PFS defined by RECIST v1.1 criteria comparing a 75-mg dose of camizestrant with 500 mg of fulvestrant and a 150-mg dose of camizestrant with fulvestrant. Secondary end points include safety, objective response rate and clinical benefit rate at 24 weeks.

A total of 240 patients have been randomly assigned to receive camizestrant or fulvestrant until disease progression.

“Our goal with our next generation oral SERD camizestrant is to improve on 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, said.

Camizestrant is being studied in multiple trials in advanced breast cancer, including the pivotal phase 3 SERENA-6 trial (NCT04964934) assessing camizestrant in combination with the CDK4/6 inhibitors palbociclib (Ibrance) and abemaciclib (Verzenio) in patients with HR-positive metastatic breast cancer who have detectable ESR1 mutations on first-line treatment, and the phase 3 SERENA-4 trial (NCT04711252) evaluating camizestrant plus palbociclib as frontline treatment in patients with HR-positive, locally advanced or metastatic breast cancer.

The indication for SERENA-6 received fast track designation from the FDA.

References

1. Camizestrant significantly improved progression-free survival vs faslodex in SERENA-2 phase II trial in advanced ER-positive breast cancer. News release. AstraZeneca. October 26, 2022. Accessed October 26, 2022. https://bit.ly/3N8lvMg
2. 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. Accessed October 26, 2022. https://clinicaltrials.gov/ct2/show/NCT04214288