Camizestrant Fails to Gain Support from the FDA’s Advisory Committee in ESR1-Mutated Advanced Breast Cancer

Clinical Summary: 

• Based on results from the phase 3 SERENA-6 trial, the FDA’s Oncologic Drugs Advisory Committee has voted that camizestrant in combination with a CDK4/6 inhibitor does not demonstrate a favorable benefit-risk profile in patients with HR-positive, HER2-negative advanced breast cancer harboring ESR1 mutations. 
• The combination significantly improved progression-free survival and time to second disease progression with favorable patient-reported outcomes, though overall survival data remain immature.
• Camizestrant introduces a ctDNA-guided early-switch strategy targeting endocrine resistance prior to progression, but its regulatory future remains uncertain. 

On April 30th, 2026, the FDA’s Oncologic Drugs Advisory Committee voted 3 to 6 that first-line camizestrant (AstraZeneca) in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor does not demonstrate a favorable benefit-risk profile among patients with HR-positive, HER2-negative advanced breast cancer harboring ESR1 mutations. 

This recommendation was based on results from the phase 3 SERENA-6 trial and will inform the FDA’s ongoing review of the New Drug Application.

In this double-blind trial, 315 patients receiving first-line treatment with an aromatase inhibitor (AI) plus palbociclib, ribociclib, or abemaciclib underwent ctDNA monitoring to detect emergent ESR1 mutations prior to disease progression. Upon detection of an ESR1 mutation, patients were randomized to switch endocrine therapy to camizestrant while continuing the same CDK4/6 inhibitor or to continue AI plus CDK4/6 inhibition. The primary end point was progression-free survival (PFS). Key secondary end points included time to second disease progression, overall survival (OS), patient-reported outcomes, and safety. 

At planned interim analysis, median PFS was 16 months in the camizestrant arm and 9.2 months in the AI arm (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.31 to 0.60; P <.00001), representing a 56% reduction in the risk of disease progression or death. At 24 months, disease control was maintained in 29.7% and 5.4% of patients, respectively. Time to second disease progression and OS data were immature, however pre-planned analysis results demonstrated that time to second disease progression was 25.7 months in the camizestrant arm and 19.1 months in the AI arm (HR, 0.63; 95% CI, 0.46 to 0.86; P = .00373). OS continued to mature in favor of the camizestrant arm.

Patient-reported outcomes showed that camizestrant consistently delayed time to deterioration in quality of life and reduced the risk of deterioration in patient-reported cancer symptoms and functioning. Camizestrant reduced the risk of deterioration in global health status and quality of life by 46% (HR, 0.54; 95% CI, 0.34 to 0.84; P <.001). Safety was consistent with prior findings. No new safety signals were identified, and treatment discontinuation rates were low and similar between arms.

“Today’s recommendation by the [Oncologic Drugs Advisory Committee] is disappointing, as new options and innovative treatment strategies which address emerging resistance ahead of disease progression and deterioration in quality of life are needed in the [first]-line setting,” stated Kevin Kalinsky, MD, MS, Winship Cancer Institute of Emory University, Atlanta, Georgia.

Source: 

AstraZeneca. Update on FDA Advisory Committee vote on camizestrant in combination with a CDK4/6 inhibitor for advanced HR-positive breast cancer. Accessed on May 4, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/fda-odac-vote-on-camizestrant-breast-cancer.html