FDA ODAC Votes No to Camizestrant for HR+/HER2– ESR1 Advanced Breast Cancer

The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 6 to 3 against the new drug application (NDA) for camizestrant for adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with emerging ESR1 mutations.¹

The question: Based on the results of SERENA-6 has clinically meaningful benefit for camizestrant been demonstrated for the treatment of patients with HR+/HER2– metastatic breast cancer with a tumor ESR1 mutation detected while on AI plus CDK4/6 prior to radiographic progression.

Camizestrant was assessed with palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio). The proposed indication focuses on patients who develop ESR1 mutations during first-line endocrine-based therapy, as detected by an FDA-approved circulating tumor DNA (ctDNA) test.

Toni Choueiri, MD, who voted yes for camizestrant noted, “Taken together, I believe camizestrant and SERENA-6 represent a favorable benefit/risk assessment, and I would be in favor.”

Choueiri is director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI), co-leader of the Kidney Cancer Program at DFCI/Harvard Cancer Center, and the Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School, and is the Medical Director, International Strategic Initiatives at DFCI.

Stanley Lipkowitz, MD, PhD, “The data for changing the paradigm just isn’t there. There is a PFS benefit, and if there was an OS benefit, I would have said yes. I agree the bar should be high here as it is changing the way we do business…I’m very excited about oral SERDs and they’re fundamentally going to change the field…I couldn’t bring myself to change the way we fundamentally treat patients based on these data.”

Lipkowitz is senior investigator of the Women's Malignancies Branch at the National Cancer Institute.

The SERENA-6 Study

The NDA is supported by data from the phase 3, double-blind, ctDNA-guided SERENA-6 trial (NCT04964934).² This global registrational study is the first to demonstrate the clinical utility of monitoring ctDNA to detect and treat emerging resistance before functional disease progression.

According to the data previously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, switching to camizestrant upon the detection of ESR1 mutations significantly improved survival outcomes compared with continuing aromatase inhibitor (AI)-based therapy:

• Progression-free survival (PFS): The median PFS was 16.0 months (95% CI, 12.7-18.2) for the camizestrant group compared with 9.2 months (95% CI, 7.2-9.5) in the AI group (HR, 0.44; 95% CI, 0.31-0.60; P <.00001).
• Time to deterioration (TTD): The median TTD was 23.0 months (95% CI, 13.8-not calculable [NC]) vs 6.4 months (95% CI, 2.8-14.0) in the AI arm (HR, 0.53; 95% CI, 0.33-0.82; P <.001).
• PFS2 (Second progression-free survival): The benefit was sustained through the next line of therapy, with 38 PFS2 events for camizestrant vs 47 for the AI arm (HR, 0.52; 95% CI, 0.33-081; P = .0038).

Study Schema:

• Patient Population: Patients on first-line AI plus CDK4/6 inhibitor therapy for at least 6 months underwent regular ctDNA surveillance using the Guardant360 CDx.
• Intervention: Upon detection of an ESR1 mutation––but before evidence of clinical or radiologic disease progression––patients were randomly assigned 1:1 to either:

1. Camizestrant at 75 mg daily while continuing the same CDK4/6 inhibitor plus placebo for AI.
2. Continuing current therapy (AI + CDK4/6 inhibitor) plus the placebo for camizestrant.

• Primary end point: PFS by investigator assessment
• Secondary end points: PFS2, overall survival, safety, and patient-reported outcomes.

Key Data and Outcomes

Baseline characteristics were well-balanced between the camizestrant arm (n = 157) and the AI arm (n = 158), with a median age of 61 years vs 60.5 years, respectively. Most patients in both arms were receiving palbociclib at the time of random assignment (76% vs 75%).

Safety Profile

Grade 3 or higher adverse effects (AEs) were noted in 60% of patients in the camizestrant arm vs 46% in the AI arm, with serious AEs observed in 10% vs 12%.

• The most common grade 3 or higher AEs included neutropenia (45% vs 34%), anemia (5% vs 5%), and leukopenia (10% vs 3%).
• Photopsia was noted to not impact any daily activities. It was noted to occur for 1 minute or less for 3 days a week or less and was reversible.

References

1. April 30, 2026 Meeting of the Oncologic Drug Advisory Committee (ODAC). Accessed April 30, 2026. https://tinyurl.com/5cry64pu
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