Detailed results from the SERENA-2 Phase II trial showed AstraZeneca’s next-generation oral selective estrogen receptor degrader (ngSERD) camizestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) at both 75mg and 150mg dose levels versus Faslodex (fulvestrant) 500mg in post-menopausal patients with estrogen receptor (ER)-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. Results will be presented today in an oral presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS).
In the overall population, camizestrant significantly reduced the risk of disease progression or death by 42% at a 75mg dose (based on a hazard ratio [HR] of 0.58, 90% confidence interval [CI] 0.41-0.81; p=0.0124; median PFS of 7.2 versus 3.7 months) and 33% at a 150mg dose (HR 0.67, 90% CI 0.48-0.92; p=0.0161; median PFS of 7.7 versus 3.7 months) compared to Faslodex, the current SERD standard of care.
Among the prespecified subgroup of patients with ESR1 mutations – comprising 36.7% of the trial population – camizestrant showed a 67% reduction in the risk of disease progression or death at a 75mg dose (HR 0.33, 90% CI 0.18-0.58; median PFS of 6.3 versus 2.2 months) and a 45% reduction at a 150mg dose (HR 0.55, 90% CI 0.33-0.89; median PFS of 9.2 versus 2.2 months) compared to Faslodex. Efficacy was also seen in patients without a detectable ESR1 mutation, with a 22% and 24% reduction in the risk of disease progression or death (HR 0.78, 90% CI 0.50-1.22 and HR 0.76, 90% CI 0.48-1.20) respectively for the 75mg and 150mg dose levels.
A clinically meaningful PFS benefit was also observed across other prespecified subgroups, including in patients previously treated with prior cyclin-dependent kinase (CDK) 4/6 inhibitors, those with lung and/or liver metastases and those with ER-driven disease.
Mafalda Oliveira, MD, PhD, Vall d’Hebron Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain, and lead investigator for the SERENA-2 Phase II trial, said: “These data reflect an important step toward a potential new treatment option for patients with advanced ER-positive disease. Based on the SERENA-2 results, camizestrant was well tolerated at both doses and significantly improved patient outcomes, nearly doubling median progression-free survival in this setting compared with the current SERD standard of care.”
Cristian Massacesi, Chief Medical Officer & Oncology Chief Development Officer, Oncology R&D, AstraZeneca, said: “SERENA-2 showed a meaningful improvement over fulvestrant, demonstrating the potential of camizestrant, our next-generation SERD, to optimise outcomes for patients with advanced ER-driven breast cancer, irrespective of ESR1 mutation status and prior treatment with CDK4/6 inhibitors. Our focus on bringing new medicines to patients across the breast cancer spectrum is unwavering and we look forward to additional findings from our ongoing Phase III development programme for camizestrant including SERENA-4 and SERENA-6.”
Summary of results: SERENA-2
