WILMINGTON, Del. — AstraZeneca said updated Phase III data showed its investigational drug camizestrant, used with a CDK4/6 inhibitor, delayed disease progression in certain patients with advanced breast cancer and produced greater reductions in circulating tumor DNA than standard treatment.
The results come from the SERENA-6 trial, which evaluated switching patients to camizestrant plus a CDK4/6 inhibitor before disease progression after an ESR1 mutation was detected. The trial enrolled patients with hormone receptor-positive, HER2-negative advanced breast cancer who had been receiving first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor.
The updated results showed the camizestrant combination reduced the risk of disease progression or death by 55% compared with continued treatment with an aromatase inhibitor and a CDK4/6 inhibitor. Median progression-free survival was 16.8 months for patients receiving the camizestrant combination, compared with 9.2 months for those who remained on the aromatase inhibitor combination.
AstraZeneca also said the camizestrant regimen reduced the risk of second disease progression or death by 37%. Median second progression-free survival was 25.7 months for the camizestrant combination, compared with 19.1 months for the comparator arm.
The company said exploratory analyses showed the camizestrant combination produced a median 99% reduction in total circulating tumor DNA by week eight, while patients who remained on standard treatment had a median 64% increase. Total ctDNA clearance was achieved by 51% of patients receiving the camizestrant combination, compared with 1.9% of patients in the standard-of-care arm.
SERENA-6 met its primary endpoint of progression-free survival at an interim analysis, with earlier results presented at the American Society of Clinical Oncology annual meeting and published in The New England Journal of Medicine. The updated results were scheduled to be presented during the 2026 ASCO Annual Meeting in Chicago.
François-Clément Bidard, MD, PhD, professor of medical oncology at Institut Curie and Versailles University in France and co-principal investigator for the trial, said the results support switching to a camizestrant-based combination in the first-line setting after the emergence of an ESR1 mutation.
“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,” Bidard said. “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 of oncology hematology research and development at AstraZeneca, said the data show the potential benefit of switching treatment before disease progression.
“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,” Galbraith said. “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.”
The company said additional analyses showed the camizestrant combination delayed the need for more intensive subsequent treatment, including chemotherapy or antibody-drug conjugates. Median chemotherapy- or antibody-drug conjugate-free survival was 22.6 months for the camizestrant combination, compared with 18.7 months for the aromatase inhibitor combination.
AstraZeneca said the safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib was consistent with the known safety profile of each medicine. No new safety concerns were identified, and discontinuation rates were low and similar in both treatment arms.
Camizestrant is an oral selective estrogen receptor degrader and complete estrogen receptor antagonist being studied in Phase III trials for HR-positive breast cancer. It is approved in the United Arab Emirates and Saudi Arabia based on the SERENA-6 trial, AstraZeneca said.
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. Regulatory applications are under review in the U.S., Japan and several other countries, and the U.S. Food and Drug Administration recently extended the review date for the application based on the updated SERENA-6 data.
