WILMINGTON, Del.--(BUSINESS WIRE)--Further positive results from the Phase III SERENA-6 trial showed AstraZeneca's camizestrant plus a cyclin-dependent kinase (CDK) 4/6 inhibitor – palbociclib, ribociclib or abemaciclib – maintained its progression-free survival (PFS) benefit with longer follow-up and delivered a statistically significant and clinically meaningful improvement in second progression-free survival (PFS2), demonstrating sustained benefit beyond initial treatment. Additionally, exploratory analyses showed that the camizestrant combination profoundly reduced total circulating tumor DNA (ctDNA) and enabled substantially more patients to achieve total ctDNA clearance.
The trial evaluated switching to the camizestrant combination before progression in the 1st-line setting versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor following detection of an ESR1 mutation in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer.
SERENA-6 met its primary endpoint of PFS at the interim analysis, with results first presented at last year’s American Society of Clinical Oncology (ASCO) and simultaneously published in The New England Journal of Medicine.1 The updated results will be presented today during the 2026 ASCO Annual Meeting in Chicago, IL (abstract LBA1007).
The updated results showed the camizestrant combination reduced the risk of disease progression or death by 55% versus an AI plus a CDK4/6 inhibitor (based on a hazard ratio [HR] of 0.45; 95% confidence interval [CI] 0.34-0.59; p<0.00001). Median PFS was 16.8 months for the camizestrant combination compared with 9.2 months for the AI combination, representing a median improvement of 7.6 months.
Importantly, the PFS benefit observed with the camizestrant combination was sustained beyond initial progression. For the key secondary endpoint of PFS2, a measure of treatment durability beyond first progression, the final PFS2 analysis showed that the camizestrant combination reduced the risk of second disease progression or death by 37% versus the comparator arm (HR 0.63; 95% CI 0.46-0.86; p=0.00373), indicating that the benefit of switching to camizestrant plus a CDK4/6 inhibitor was maintained even after patients received subsequent therapies. Median PFS2 was 25.7 months for the camizestrant combination compared with 19.1 months for the AI combination.
The camizestrant combination also demonstrated substantially greater reductions in total ctDNA in blood than continued treatment with an AI plus a CDK4/6 inhibitor at week 4 and/or week 8 after randomization. Patients who switched to the camizestrant combination had a median 99% reduction in total ctDNA by week 8, with 51% achieving total ctDNA clearance, compared with a median 64% increase in total ctDNA by week 8, and 1.9% total ctDNA clearance among patients who remained on the AI combination. These results show the early effect of switching to camizestrant on ctDNA which is linked to tumor burden reduction.
Clearance of total ctDNA during treatment has been associated with long-term clinical benefit including improved overall survival (OS) across tumor types, including in patients with HR-positive, HER2-negative advanced breast cancer receiving endocrine-based therapy plus a CDK4/6 inhibitor.2,3 In an exploratory analysis pooled across both arms in SERENA-6, total ctDNA clearance was associated with OS benefit (HR 0.39; 95% CI 0.19-0.73), consistent with other studies.
Data for the key secondary endpoint of OS showed a numerical trend favoring the camizestrant combination (HR 0.87; CI 0.57-1.30) at 30% maturity. The trial will continue to final analysis to assess OS.
François-Clément Bidard MD, PhD, Professor of Medical Oncology at Institut Curie & Versailles University (Paris/Saclay) France and co-principal investigator for the trial, said: “Optimizing outcomes for patients with HR-positive advanced breast cancer early in their treatment is critical because once the disease progresses, it becomes harder to treat and outcomes worsen. The updated SERENA-6 results support the paradigm of switching to a camizestrant-based combination in the first-line setting upon emergence of an ESR1 mutation and demonstrate durable improvements beyond initial treatment. These results should change how we approach treating patients with HR-positive disease in the first-line setting.”
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “More than half of patients who switched to the camizestrant combination completely cleared tumor DNA from their bloodstream compared to two percent with standard of care. This provides robust evidence that an early treatment switch has strong anti-tumor efficacy, and supports the potential for long-term clinical benefit. Switching to the camizestrant combination also extended the time patients lived without disease progression after first- and second-line treatment, delayed the need for more intensive therapies, and helped patients maintain their quality of life. Together, these results add to the growing data supporting the potential of the camizestrant combination to improve outcomes for these patients with advanced breast cancer.”
Summary of results: SERENA-6 at ASCO 2026
Camizestrant + CDK4/6 inhibitor
AI + CDK4/6 inhibitor
PFSi
Number of patients (n)
157
158
Median PFS (months)
16.8 (14.7-19.4)
9.2 (7.2-9.7)
24-month PFS rate
34.9%
14.2%
Hazard ratio (95% CI)
0.45 (0.34-0.59)
p-value
p<0.00001
PFS2ii
Number of patients (n)
157
158
Median PFS2 (months)
25.7 (20.4-30.3)
19.1 (16.8-21.0)
24-month PFS2 rate
50.8%
36.3%
Hazard ratio (95% CI)
0.63 (0.46-0.86)
p-value
p=0.00373
OSiii
Events, n (%)
46 (29.3)
49 (31.0)
Hazard ratio (95% CI)
0.87 (0.57-1.30)
Change in total ctDNA
Median change from baseline at week 8
-99%
+64%
Total ctDNA clearanceiv
Number of patients with clearance/total analyzed
50/98
2/108
Patients with total ctDNA clearance (%)
51.0
1.9
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; PFS2, progression-free survival 2; OS, overall survival
Additional analyses showed that the camizestrant combination delayed the need for more intensive subsequent treatment, including chemotherapy or antibody-drug conjugates (ADCs). Median chemotherapy/ADC-free survival was 22.6 months for the camizestrant combination versus 18.7 months for the AI combination (HR 0.64; 95% CI 0.47-0.87; p=0.00375). The camizestrant combination was also associated with delayed deterioration in patient-reported cancer symptoms such as pain, global health status and quality of life.
The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in the SERENA-6 trial was consistent with the known safety profile of each medicine. No new safety concerns were identified, and discontinuations were very low and similar in both arms.
Camizestrant is approved in the United Arab Emirates and Saudi Arabia based on the SERENA-6 trial. The European Medicines Agency’s Committee for Medicinal Products for Human Use recently adopted a positive opinion recommending approval of the camizestrant combination in the European Union based on the results of the SERENA-6 Phase III trial.
Regulatory applications are also currently under review in the US, Japan and several other countries. The US Food and Drug Administration last week extended the Prescription Drug User Free Act date to review the updated results from the SERENA-6 trial.
Notes
HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.4 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.4 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.5
HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative.5 More than 97% of HR-positive breast cancer tumors are estrogen receptor (ER)-positive. ERs often drive the growth of HR-positive breast cancer cells.6
Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target ER-driven disease, which are often paired with CDK4/6 inhibitors.7-9 However, resistance to these therapies develops in many patients.9 Once this occurs, treatment options are limited and survival rates are low with approximately 36% of patients anticipated to live beyond five years after diagnosis.5,9
Mutations in the ESR1 gene are a key driver of endocrine resistance and are associated with poor outcomes, emerging during treatment of the disease and becoming more prevalent as the disease progresses.10,11 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment before disease progression.7
The optimization of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.
SERENA-6
SERENA-6 is a Phase III, double-blind, randomized trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumors have an emergent ESR1 mutation.
The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment.
SERENA-6 is the first global, registrational Phase III trial to use a circulating tumor DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The innovative trial design used ctDNA monitoring via a blood test at the time of routine tumor scans every two to three months to identify patients for early signs of endocrine resistance via the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor.
Camizestrant
Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer.
AstraZeneca’s broad, robust and innovative clinical development program, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative breast cancer.
Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated a statistically significant and clinically meaningful improvement in PFS versus fulvestrant in the overall trial population, including in patients with ESR1 tumor mutations irrespective of prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment.
With fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant.
PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc., known as MSD outside the US and Canada, continue to research olaparib in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of datopotamab deruxtecan-dlnk alone and in combination with immunotherapy durvalumab.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.
References
Bidard FC, et al. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. N Engl J Med 2025; DOI: 10.1056/NEJMoa2502929.
Chia SKL, et al. On-treatment (tx) dynamic circulating tumor DNA changes (∆ctDNA) associated with progression-free survival (PFS) and overall survival (OS) of patients (pts) with HR+/HER2− advanced breast cancer (ABC) in MONALEESA-3 (ML-3). J Clin Oncol 2024;42(16_suppl):1012.
Fuentes-Antrás J, et al. Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy. npj breast cancer 2025;11:74.
Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 2024; 1- 35. DOI:10.3322/caac.21834.
National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html . Accessed June 2026.
Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun . 2022; 10.1038/s41467-022-30898-0.
Cerner CancerMPact database. Accessed June 2026.
Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer . 2020; 10.7150/jca.48944.
Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res . 2022; 28(5):821-30.
Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res . 2021; 23:85.
Zundelevich A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res . 2020; 22:16.
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