European Commission Approves Camizestrant Plus CDK4/6 Inhibition for Emergent ESR1-Mutated Advanced Breast Cancer

The European Commission has approved camizestrant (Etcamah) plus a CDK4/6 inhibitor for the treatment of adult patients with estrogen receptor (ER)–positive, HER2-negative locally advanced or metastatic breast cancer upon the detection of an ESR1 mutation and without disease progression during frontline endocrine therapy in combination with a CDK4/6 inhibitor.¹

The decision follows a positive opinion from the European Union’s Committee for Medicinal Products for Human Use and covers use with palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio).

The approval was supported by findings from the phase 3 SERENA-6 trial (NCT04964934), which were presented at the 2025 ASCO Annual Meeting.^1,2 At a planned interim analysis, patients who switched to camizestrant plus a CDK4/6 inhibitor upon the development of an ESR1 mutation in circulating tumor DNA (ctDNA; n = 157) achieved a median progression-free survival (PFS) of 16.0 months (95% CI, 12.7-18.2) vs 9.2 months (95% CI, 7.2-9.5) among those who continued an aromatase inhibitor plus a CDK4/6 inhibitor (n = 158), translating to a 56% reduction in the risk of disease progression or death (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).

“Today’s approval is welcome news for the 1 in 3 patients in Europe with this form of advanced breast cancer whose tumors develop ESR1 mutations before disease progression and are in urgent need of new options that both delay this progression and extend the benefit of first-line treatments,” François-Clément Bidard, MD, PhD, stated in a news release.¹ “As the first pivotal trial to demonstrate the clinical value of monitoring ctDNA in the first-line breast cancer setting, SERENA-6 represents a significant advance in clinical practice, and it is now important to identify patients who may be able to benefit from this combination and intervene promptly before their disease progresses.”

Bidard is a professor of medicine in the Department of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay. He is also the co-coordinator of breast cancer research and director of the Clinical Investigation Center at Institut Curie, as well as the medical director for Breast Oncology at the Women’s Cancer Institute. He also served as a co-principal investigator of the trial.

How was the SERENA-6 trial designed?

SERENA-6 was a global, double-blind, randomized trial that enrolled 315 adult patients with histologically confirmed hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who were receiving an aromatase inhibitor plus a CDK4/6 inhibitor as first-line treatment.² ctDNA was assessed via blood test at the time of routine tumor scans every 2 to 3 months to detect emergent ESR1 mutations. Patients in whom an ESR1 mutation was detected without disease progression were randomly assigned to switch their endocrine backbone to camizestrant or continue the aromatase inhibitor, in both cases maintaining the same CDK4/6 inhibitor.

Investigator-assessed PFS served as the primary end point. Secondary end points included overall survival (OS) and time to second disease progression (PFS2) by investigator assessment.

What additional efficacy data were reported from SERENA-6?

The PFS2 and OS data were immature at the time of the interim analysis. A subsequent preplanned analysis presented at ASCO 2026 showed a median PFS2 of 25.7 months (95% CI, 20.4-30.3) with the camizestrant combination vs 19.1 months (95% CI, 16.8-21.0) with the aromatase inhibitor combination (HR, 0.63; 95% CI, 0.46-0.86; P = .00373).³ The OS data continued to mature in favor of the camizestrant combination (HR, 0.87; 95% CI, 0.57-1.30), and the trial will continue to evaluate OS as a key secondary end point.¹

What are the safety profile and global regulatory status of camizestrant?

The safety profile of camizestrant in combination with palbociclib, ribociclib, or abemaciclib in SERENA-6 was consistent with the known profiles of each agent, no new safety concerns were identified, and treatment discontinuation rates were low and similar between the 2 arms.¹

Camizestrant is also approved in this setting in Japan, the United Arab Emirates, and Saudi Arabia. Regulatory applications are under review in several additional countries, including the United States, where the FDA extended the Prescription Drug User Fee Act target action date for the new drug application to review updated data from the trial.⁴ Notably, in April 2026, the FDA’s Oncologic Drugs Advisory Committee failed to reach a majority vote in favor of the benefit-risk profile of the camizestrant combination in this indication.⁵

References

1. Etcamah (camizestrant) in combination with a CDK4/6 inhibitor approved in the EU for 1st-line advanced ER-positive breast cancer. News release. AstraZeneca. July 23, 2026. Accessed July 23, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/
2. Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4
3. Bidard F-C, Mayer E, Park YH, et al. First-line camizestrant for emergent ESR1 mutations in advanced breast cancer: final progression-free survival results 2 from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 17):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007
4. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed July 23, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html
5. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed July 23, 2026. https://www.youtube.com/live/taCx7enN7hk