AstraZeneca’s Camizestrant Shows Survival Improvement for HR-Positive, HER2-Negative Advanced Breast Cancer with Emergent ESR1 Mutations

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Results from the Phase III SERENA-6 trial demonstrated that AstraZeneca’s camizestrant in combination with a CDK4/6 inhibitor significantly improved progression-free survival (PFS) in the first-line treatment of HR-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations. The study is the first global trial to use a circulating tumor DNA-guided (ctDNA) approach to detect endocrine resistance before disease progression.¹

“Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies. The results from SERENA-6 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 delays progression of disease and extends the benefit of first-line treatment, representing an important step forward for patients, and a potential shift in clinical practice,” said François-Clément Bidard, MD, PhD, professor of medical oncology, Institut Curie & UVSQ/Université Paris-Saclay, France, co-principal investigator for the trial, in the press release.

The double-blind, randomized SERENA-6 trial compared the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) vs. standard-of-care treatment with an aromatase inhibitor plus a CDK4/6 inhibitor. The study enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer who were undergoing treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. The primary endpoint of the study is PFS as assessed by investigator, with secondary endpoints including overall survival (OS) and second disease progression (PFS2).

Investigators noted that OS and PFS2 data are immature, but early results suggest a positive trend. Camizestrant’s safety profile in combination with palbociclib, ribociclib, or abemaciclib was consistent with each treatment’s previously established profile and no new safety signals were identified. Additionally, the discontinuation rate was low in both arms of the study.¹

According to the American Cancer Society, breast cancer is the most common cancer in women in the United States outside of skin cancers. It is estimated that by the end of 2025, there will be 316,950 new cases of invasive breast cancer diagnosed in women in the United States, with 42,170 deaths expected. On average, the probability of US women getting breast cancer is 13%, equal to a one in eight chance.

Breast cancer is most common in middle-aged and older women, with a median diagnosis age of 62 years. However, a small number of women can be diagnosed under 45 years of age. Within the past few years, incidence rates have increased by 1% annually, mainly due to excess weight, more women having children after 30 years of age, and not having children altogether.

Breast cancer is currently the second leading cause of cancer-related deaths in women, behind lung cancer, with a 2.3% chance of mortality; however, mortality rates decreased 44% between 1989 and 2022.²

"These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumors develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This critical read-out moves us one step closer to realizing the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer,” said Susan Galbraith, EVP, oncology, hematology R&D, AstraZeneca, in the press release.

Full data from SERENA-6 will be presented at an upcoming medical meeting and shared with regulatory authorities.¹

References

1. Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial. AstraZeneca. February 26, 2025. Accessed February 27, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html

2. Key Statistics for Breast Cancer. American Cancer Society. Accessed February 27, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html