Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) being developed for ER-positive, HER2-negative advanced breast cancer. The Phase III SERENA-6 trial evaluated camizestrant plus CDK4/6 inhibitor therapy in patients with emergent ESR1 mutations detected by circulating tumor DNA during first-line aromatase inhibitor plus CDK4/6 inhibitor treatment, prior to radiographic progression. These results support camizestrant as a potential next-generation SERD and highlight a shift toward ctDNA guided, early intervention strategies in ESR1-mutant disease. 

The US FDA has extended the PDUFA action date for AstraZeneca’s NDA of camizestrant in combination with a CDK4/6 inhibitor for first-line treatment of HR-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations, to seek additional data. The FDA's Oncologic Drugs Advisory Committee did not reach a majority vote in favour of the benefit of switching to camizestrant in combination with a CDK4/6 inhibitor after detection of an ESR1 mutation in circulating tumour DNA (ctDNA) prior to radiographic progression, based on the SERENA-6 phase III trial. Subsequently, the company has provided additional analyses requested by the FDA in support of the application, including ctDNA clearance data linked to longer-term efficacy outcomes. 

AstraZeneca’s camizestrant plus a CDK4/6 inhibitor has been recommended for EU approval in ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation after first-line endocrine therapy without progression.

The safety profile of camizestrant combined with palbociclib, ribociclib, or abemaciclib in the SERENA-6 trial was consistent with the established safety profiles of each agent. No new safety signals were observed, and treatment discontinuation rates were low and comparable between both study arms.

KOL insights

“Optimising 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.” –Expert Opinion

“More than half of patients who switched to the camizestrant combination completely cleared tumour DNA from their bloodstream compared to two per cent with standard of care. This provides robust evidence that an early treatment switch has strong anti-tumour 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.”–Expert Opinion

Conclusion

Breast cancer is the most common cancer among women in the United States. In 2025, there are an estimated ~693,000 incident cases of HR-positive (HR+). The United States accounts for approximately ~44% of the 7MM prevalent HR+ breast cancer population.

In the broader competitive landscape, CDK4/6 inhibitor–based endocrine therapy (palbociclib, ribociclib, abemaciclib combinations) remains the established first-line backbone. Upon endocrine resistance, the current treatment ecosystem includes oral SERDs such as elacestrant, next-generation SERDs (camizestrant), and targeted therapies such as PI3K/AKT pathway inhibitors, which are primarily used after progression. ADCs are used in later-line settings in HR-positive advanced breast cancer but are not part of the first-line endocrine therapy backbone. Overall, SERENA-6 supports a shift from radiographic progression-driven treatment decisions to ctDNA-guided, biology-driven early intervention, positioning camizestrant as a potential sequencing strategy for ESR1-mutant disease. However, CDK4/6 inhibitor–based regimens remain the standard of care.