AstraZeneca Details Its Oral SERD ‘Switching’ Regimen Amid Feasibility Questions

AstraZeneca has reported Phase 3 data from the SERENA-6 trial, investigating the feasibility of an oral SERD (selective estrogen receptor degrader) 'switching' regimen using camizestrant in patients with advanced HR-positive breast cancer who develop ESR1 tumor mutations while on standard aromatase inhibitor and CDK4/6 inhibitor therapy13.

When patients with emergent ESR1 mutations were switched early from standard-of-care aromatase inhibitors to camizestrant (combined with a CDK4/6 inhibitor), the risk of disease progression or death was reduced by 56% compared to those who continued the standard regimen123.

Though data for secondary endpoints like overall survival (OS) and time to second disease progression (PFS2) were still immature at the interim analysis, a positive trend was seen supporting the combination's benefit, especially in delaying treatment failure and maintaining quality of life3.

The results are viewed as a potential paradigm shift in managing resistance:
proactively switching therapy after detection of an ESR1 mutation, before clinical progression, may extend the benefit of first-line treatment and improve patient outcomes3.

Despite promising efficacy, questions about the real-world feasibility of this early 'switching' approach remain, particularly regarding the logistics and costs of mutation monitoring and whether such biomarker-guided strategies are practical to implement outside trial settings1.

Sources:

1. https://endpts.com/asco25-astrazeneca-details-phase-3-data-for-oral-serd-switching-regimen/

2. https://firstwordpharma.com/story/5967776

3. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-reduced-the-risk-of-disease-progression-or-death-by-56-in-patients-with-advanced-hr-positive-breast-cancer-with-an-emergent-esr1-tumour-mutation-in-serena-6-phase-iii-trial.html