AstraZeneca's experimental breast cancer drug camizestrant has demonstrated a 56% reduction in the risk of disease progression or death when treatment decisions are guided by liquid biopsy testing, according to results from the global SERENA-6 Phase III trial presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The randomized, multicentre, double-blind trial evaluated camizestrant, an investigational next-generation oral selective estrogen receptor degrader (SERD), in combination with CDK4/6 inhibitors versus standard-of-care treatment in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who developed detectable ESR1 mutations.
Breakthrough in Precision Medicine Approach
The SERENA-6 study represents the first global trial to demonstrate that using circulating tumor DNA (ctDNA) blood tests to guide treatment changes before clinical signs of progression appear provides significant clinical benefit. This proactive approach allows clinicians to detect emerging resistance and intervene before tumors have a chance to grow and make patients unwell.
"This is a pivotal moment in breast cancer care," said Professor Nick Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and co-principal investigator of the study. "These results demonstrate that using liquid biopsy blood tests to spot emerging resistance in tumours, before they start to grow and make the patient unwell, can guide early intervention with camizestrant to delay disease progression in patients with ESR1 mutations."
Trial Design and Patient Population
The study screened 3,325 patients with HR-positive, HER2-negative advanced breast cancer from 23 countries who had been on first-line treatment for at least six months. Patients underwent ctDNA testing every 8-12 weeks to monitor for ESR1 mutations. Of those screened, 548 patients tested positive for ESR1 mutations during the screening period, and 315 were randomized into the study.
ESR1 mutations are a key driver of resistance that can develop during or after endocrine treatment, emerging in approximately 40% of patients treated with aromatase inhibitors. These mutations allow cancer to grow and resist hormone-blocking treatments, making them a critical target for intervention.
Significant Clinical Outcomes
Half of the randomized patients received camizestrant alongside their CDK4/6 inhibitor, while the control group continued with their aromatase inhibitor and CDK4/6 inhibitor. The results showed that the camizestrant combination extended median progression-free survival to 16 months compared to 9.2 months for patients on the control arm, representing a hazard ratio of 0.44.
The treatment was well tolerated, with only 1% of patients experiencing side effects that led to treatment discontinuation. Additionally, the therapy reduced the risk of deterioration in patients' general health and quality of life by 47% compared to the control group, demonstrating the benefit of keeping patients on first-line therapy longer.
Market Context and Competition
Hormone receptor-positive, HER2-negative breast cancer is the most common subtype diagnosed in developed countries. According to GlobalData, the number of diagnosed incident cases of invasive hormone receptor-positive/HER2-negative breast cancer in women across eight major markets will grow from 625,674 in 2025 to 648,377 in 2028.
AstraZeneca faces competition in the oral SERD space from several companies. Roche's giredestrant is undergoing five Phase III trials, while Arvinas/Pfizer's vepdegestrant is being investigated in Phase III trials with expected completion in August 2028. Eli Lilly's imlunestrant has also shown positive results for patients with HR-positive/HER2-negative breast cancer with ESR1 mutation status.
According to GlobalData's analyst consensus forecast, global sales of camizestrant are expected to reach $982 million by 2030, compared to projected sales of $1.10 billion for giredestrant and $1.13 billion for vepdegestrant.
Clinical Impact and Future Implications
"When patients progress on scans, we're already behind," said Dr. Eleonora Teplinsky, an oncologist at Valley-Mount Sinai Comprehensive Cancer Care and ASCO breast cancer expert. "An early switch approach, before disease progression, allows doctors to essentially stay ahead of the curve."
The findings have the potential to establish a new treatment strategy for patients with this common type of advanced breast cancer, potentially delaying the need for chemotherapy and its associated toxic side effects. AstraZeneca is positioning camizestrant as a first-line therapy and is conducting five Phase III trials for the drug in breast cancer.
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, emphasized the transformational nature of the results: "The results of the SERENA-6 trial represent more than a clinical milestone – they represent a transformational shift in how we approach precision medicine."
The study results were simultaneously published in The New England Journal of Medicine, marking a significant milestone in the development of personalized breast cancer treatment strategies.
