FDA Approves Camizestrant for ESR1-Mutated HR+/HER2– Advanced Breast Cancer

The News

The FDA has approved camizestrant (Etcamah) for adult patients with hormone receptor (HR)–positive, HER2-negative locally advanced or metastatic breast cancer with emerging ESR1 mutations detected during first-line aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy, according to a news release from the agency.¹

The approval marks a reversal from the FDA’s Oncologic Drugs Advisory Committee (ODAC), which voted 6 to 3 against the new drug application for camizestrant in April 2026, concluding that data available at the time did not demonstrate a clinically meaningful benefit for patients whose ESR1 mutations were detected via circulating tumor DNA (ctDNA) before radiographic disease progression.² The FDA subsequently delayed its regulatory decision in May 2026 to review supplemental ctDNA clearance analyses submitted by the drug's developer, AstraZeneca, ahead of the presentation of updated survival data at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.^3,4

What data support the approval?

The final progression-free survival 2 (PFS2) results from the phase 3 SERENA-6 trial (NCT04964934) showed that switching to camizestrant upon detection of emergent ESR1 mutations extended median PFS by 7.6 months compared with continuing the same AI-based regimen. At the third data cutoff, with a median follow-up of 23.5 months, camizestrant plus CDK4/6 inhibitor therapy reduced the risk of disease progression or death by 55% relative to continued AI plus CDK4/6 inhibitor therapy (HR, 0.45; 95% CI, 0.34-0.59; P <.00001). The median PFS was 16.8 months with camizestrant compared with 9.2 months in the control arm, and 34.9% of patients receiving camizestrant remained progression free at 24 months vs 14.2% of those who continued AI-based therapy.

PFS2, a prespecified key secondary end point measuring time to second progression or death, reached statistical significance, favoring camizestrant plus CDK4/6 inhibitor therapy with a median of 25.7 months vs 19.1 months for continued AI-based therapy (HR, 0.63; 95% CI, 0.46-0.86; P = .00373). The early-switch approach also delayed the need for chemotherapy or antibody-drug conjugate therapy by a median of 3.9 months. The PFS benefit was consistent across common co-mutations, including PIK3CA and TP53, and was similarly observed in patients with single or multiple ESR1 mutations. In an exploratory analysis, ctDNA clearance by week 8, achieved in 51% of evaluable patients receiving camizestrant vs 1.9% of those in the control arm, was associated with an overall survival benefit (HR, 0.39; 95% CI, 0.19-0.73).

How was SERENA-6 designed?

SERENA-6 enrolled 315 patients with ER-positive, HER2-negative advanced breast cancer who had received an AI plus a CDK4/6 inhibitor (palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio]) as initial endocrine-based therapy for at least 6 months, had an ESR1 mutation detected in ctDNA with no evidence of disease progression, and had received no more than 1 prior line of chemotherapy for advanced disease. Patients were randomly assigned 1:1 to camizestrant at 75 mg once daily plus continuing CDK4/6 inhibitor therapy or to continued AI plus CDK4/6 inhibitor therapy.

What is the safety profile?

The combination was well tolerated, with no new safety signals identified at the final analysis. Grade 3 or higher adverse effects were reported in 60% of patients in the camizestrant arm vs 46% in the AI-continuation arm, with neutropenia (45% vs 34%) and leukopenia (10% vs 3%) among the most common. Photopsia was reversible, brief, and did not affect daily activities in reported cases.

Camizestrant is already approved in the European Union under the brand name Etcamah following a positive opinion from the Committee for Medicinal Products for Human Use.⁵

References

1. FDA grants accelerated approval to a new breast cancer treatment. News release. FDA. September 4, 2026. Accessed September 4, 2026. https://tinyurl.com/ym8hw67u
2. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). YouTube. Accessed April 30, 2026. https://tinyurl.com/5cry64pu
3. FDA delays ruling on AstraZeneca's breast cancer drug after negative adcomm vote. Fierce Biotech. May 27, 2026. Accessed September 3, 2026. https://tinyurl.com/y6rhjxav
4. Bidard FC, Mayer EL, Park YH, et al. First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer: final progression-free survival 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
5. Etcamah (camizestrant) in combination with a CDK4/6 inhibitor approved in the EU for 1st-line advanced ER-positive breast cancer. News release. July 23, 2026. Accessed September 3, 2026. https://tinyurl.com/fmbpurb6