FDA Approves Camizestrant for ER+, HER2– mBC With ESR1 Mutations

FDA late today granted accelerated approval to camizestrant for firstline treatment of patients with ER-positive, HER2-negative metastatic breast cancer with ESR1 mutations.¹ The action comes more than 3 months after regulators delayed a decision on the therapy, following a thumbs down from an advisory committee.²

AstraZeneca announced the approval in statement.¹

To be sold as Etcamah, camizestrant is approved for use in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (abemaciclib, palbociclib or ribociclib) for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer upon detection of ESR1 mutation during aromatase inhibitor (AI) and CDK4/6 inhibitor therapy, based on an FDA-approved test.¹

In doing so, the FDA reversed course, following a 6-3 vote by the Oncologic Drugs Advisory Committee (ODAC) against recommending approval.² Panelists had questioned the core thinking behind the evidence backing the drug, which called for switching to a new treatment based on signals from a blood test rather than physical disease progression.

Camizestrant is an oral, next-generation selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist that stops cancer cell growth by binding to estrogen receptors, causing them to break down. Although there has been much excitement among oncologists for the drug itself, the strategy behind the phase 3 SERENA-6 trial (NCT04964934), presented in June 2025 at the plenary session of the American Society of Clinical Oncology annual meeting, has stirred considerable debate.

Following the trial strategy, AstraZeneca sought approval to switch out the aromatase inhibitor for camizestrant upon detecting an emerging ESR1 mutation in circulating tumor DNA (ctDNA), even before patients showed standard radiographic (X-ray/scan) disease progression. Patients would be treated with a CDK4/6 inhibitor throughout.

Late Friday, supporters of the FDA approval took note of differing opinions on social media and urged clinicians to follow forthcoming trial results. As Erika Hamilton, MD, FASCO, director of Breast Cancer Research Programs at Sarah Cannon Research Institute posted on LinkedIn, “the data matures as we go.”

Trial Results Strongly Favor Camizestrant

In June 2025, data from the study were reported in the New England Journal of Medicine.³ The primary outcome was investigator-assessed progression-free survival (PFS). Patients were treated on an aromatase inhibitor and a CDK4/6 inhibitor for at least 6 months before receiving an FDA-approved test (the Guardant360 CDx assay) to detect an ESR1 mutation. These mutations cause ER-positive tumors to become resistant to standard hormonal therapies by locking the receptor in an active state, allowing the cancer to multiply even when estrogen levels are reduced to zero.⁴

According to the study authors, patients were eligible to participate in the randomized portion of the trial if they had:

1. a detectable ESR1 mutation without evidence of disease progression,
2. had an ECOG performance-status score of 0 or 1, and
3. had at least 1 evaluable lesion for baseline and repeat assessments.

During the surveillance period, ESR1 testing occurred every 2 to 3 months. Results showed the following:³

• Among 3256 patients who were tested for an ESR1 mutation, 315 eligible patients were assigned to switch to camizestrant (157 patients) or stay on an aromatase inhibitor (158 patients).
• At the interim analysis, the median PFS was 16.0 months for camizestrant vs 9.2 months for the aromatase-inhibitor group, for a hazard ratio (HR) of 0.44 for progression or death (95% CI, 0.31 to 0.60; P < .0001).
• According to NEJM, the median time until “deterioration in the patient-reported global health status and quality of life occurred” was 21.0 months with camizestrant vs 6.4 months among those who continued with an aromatase inhibitor (HR, 0.54; 95% CI, 0.34 to 0.84).
• Frequency of discontinuation due to adverse events was 1.3% with camizestrant vs 1.9% with an aromatase inhibitor.

ODAC and EMA Regulators View Data Differently

Members of FDA’s ODAC saw exciting potential with camizestrant, but without overall survival (OS) data, a majority could not justify a fundamental change to their criteria for approving therapies. During the April 30, 2026, meeting, the panel found that SERENA-6 did not meet the bar for offering patients “clinically meaningful benefit.”⁵

Stanley Lipkowitz, MD, PhD, of the National Cancer Institute, said he voted no because he felt the data were not there to change the paradigm.

“There is a progression-free survival benefit—if there was an overall survival benefit, I think I would have voted yes, for sure,“ Lipkowitz said.⁵ “Aside from OS, I don’t see how they can demonstrate [the benefit of] early vs late [treatment] at this point.

He added, “I agree that the bar should be high here, because it’s changing fundamentally the way we do business, and I do agree with the FDA’s concern that all the [subsequent] trials will do exactly this, with no evidence that [early treatment switch] is improving outcomes.”

The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) saw things differently. That panel offered a positive opinion and recommended marketing authorization, which the European Commission granted in July 2026.⁶

“The combination provides an important new option for the 1 in 3 patients with this form of advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression,” Kevin Kalinsky, MD, MS, FASCO, division director of Medical Oncology, Winship Cancer Institute of Emory University and investigator for the trial, said in the statement.¹ “Today’s approval will enable clinicians to promptly intervene and change therapeutic strategy at an earlier opportunity ahead of disease progression, rather than waiting until the cancer becomes harder to treat, and patient outcomes and quality of life worsen.”

References

1. ETCAMAH® (camizestrant) in combination with a CDK4/6 inhibitor approved in the US for 1st-line advanced HR-positive breast cancer. News release. AstraZeneca. September 4, 2026. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2026/ETCAMAH-camizestrant-in-combination-with-a-CDK-4-6-inhibitor-approved-in-the-US-for-1st-line-advanced-HR-positive-breast-cancer.html
2. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed August 13, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html
3. Bidard F-C. Mayer EL, Park YH, et al, for the SERENA-6 Study Group. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med. 2025;393:569-80. DOI: 10.1056/NEJMoa2502929
4. Kaklamani V. ESR1 mutation testing. Living Beyond Breast Cancer. Accessed August 13, 2026. https://www.lbbc.org/about-breast-cancer/testing/biomarker/ctdna/esr1-mutation
5. Ryan C. FDA ODAC votes against clinical benefit of switching to camizestrant in HR+ breast cancer after ESR1 mutation detection. OncLive. April 30, 2026. Accessed August 13, 2026. https://www.onclive.com/view/fda-odac-votes-against-clinical-benefit-of-switching-to-camizestrant-in-hr-breast-cancer-after-esr1-mutation-detection
6. 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 August 13, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/etcamah-approved-eu-for-er-breast-cancer.html