Key Takeaways
- Camizestrant Combo Halved Risk of Progression: AstraZeneca’s camizestrant plus a CDK4/6 inhibitor cut the risk of disease progression or death by 56% vs. standard aromatase inhibitor (AI)-based therapy in HR+/HER2- breast cancer with ESR1 mutations.
- Substantial Quality-of-Life Benefit Observed: Median time to quality-of-life deterioration was nearly three times longer with camizestrant at 23.0 months vs. 6.4 months for AI therapy.
- No New Safety Signals Identified: Despite a higher rate of grade ≥3 adverse events, the camizestrant combination maintained a manageable safety profile in line with known CDK4/6 toxicities.
Results from the Phase III SERENA-6 trial show that AstraZeneca’s camizestrant, a next-generation oral SERD, combined with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib), significantly reduced the risk of disease progression or death compared to standard aromatase inhibitor (AI)-based therapy in patients with HR-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations. Results were presented at the 2025 American Society of Clinical Oncology Annual Meeting.1
Could Camizestrant Set a New Standard for Treating HR-Positive Breast Cancer with ESR1 Mutations?
“Today’s news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer,” SERENA-6 co-principal investigator Nicholas Turner, MD, PhD, professor, molecular oncology, the Institute of Cancer Research, London, the Royal Marsden NHS Foundation Trust, said in a press release. “The results of the innovative SERENA-6 trial show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimize patient outcomes.”
How was the SERENA-6 Trial Designed to Assess Camizestrant’s Effectiveness?
- The double-blind, randomized SERENA-6 trial evaluated the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor compared to treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in 315 patients.
- The primary endpoint of the study was progression-free survival (PFS) as assessed by investigator, while secondary endpoints included overall survival (OS) and PFS2 as assessed by investigator.
What were the Efficacy Outcomes for Camizestrant versus Aromatase Inhibitors?
- Results show that the camizestrant combination reduced the risk of disease progression or death by 56%.
- Median PFS was 16 months in the camizestrant arm compared to 9.2 months in the AI arm.
- Time to deterioration in global health status/quality of life was 23 months in the camizestrant arm and 6.4 months in the AI arm.
- For PFS2, the camizestrant arm had 38 events, while the AI arm had 47 events.
Safety Profile & Adverse Events
- Sixty percent of patients experienced adverse events (AEs) of grade 3 or higher in the camizestrant arm compared to 46% in the AI arm.
- The majority of AEs were hematological events associated with CDK4/6 inhibitor treatment and included neutropenia, anemia, and leukopenia.
- Discontinuation rates were low in both arms, with 1% discontinuing in the camizestrant arm and 2% in the AI arm.
- The safety profile of the combination treatment was found to be consistent with the known safety profile of each individual treatment, with no new safety signals identified.1
How do These Results Compare to Other Emerging Endocrine Therapies?
AstraZeneca wasn’t the only company to announce promising breast cancer data at ASCO. Pfizer and Arvinas also reported that vepdegestrant, an investigational oral PROTAC ER degrader, significantly improved PFS compared to fulvestrant in patients with ER-positive/HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations.2
“As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer,” said Susan Galbraith, EVP, oncology, hematology R&D, AstraZeneca, in the press release. “Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer.”
References
1. Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial. AstraZeneca. June 1, 2025. Accessed June 5, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-reduced-the-risk-of-disease-progression-or-death-by-56-in-patients-with-advanced-hr-positive-breast-cancer-with-an-emergent-esr1-tumour-mutation-in-serena-6-phase-iii-trial.html
2. Pfizer, Arvinas’ Novel PROTAC ER Degrader Shows Significant Survival Benefit in ER+/HER2- Advanced Breast Cancer. PharmExec. June 5, 2025. Accessed June 5, 2025. https://www.pharmexec.com/view/pfizer-arvinas-novel-protac-er-degrader-significant-survival-benefit-er-her2-advanced-breast-cancer
