The Babak Lab shared on LinkedIn:
“FDA approves a new treatment strategy for ESR1-mutated breast cancer.
The FDA has granted accelerated approval to camizestrant (Etcamah) in combination with a CDK4/6 inhibitor – abemaciclib, palbociclib, or ribociclib for adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer who develop an ESR1 mutation during aromatase inhibitor + CDK4/6 inhibitor therapy.
Key Insights
- The approval is based on the Phase 3 SERENA-6 trial, which included 315 patients.
- Instead of continuing the same aromatase inhibitor after an ESR1 mutation is detected, patients switched to camizestrant while continuing their CDK4/6 inhibitor.
- Median progression-free survival was 16 months with camizestrant + CDK4/6 inhibitor versus 9.2 months with continued aromatase inhibitor + CDK4/6 inhibitor.
- This corresponds to a 56% reduction in the risk of disease progression or death (HR 0.44; p < 0.00001).
- ESR1 mutations were detected through circulating tumor DNA (ctDNA) testing, using the FDA-approved Guardant360 CDx companion diagnostic.
Why it matters
The approval highlights a more adaptive approach to endocrine therapy: rather than waiting for clinical progression, treatment can be changed when an emerging molecular resistance mechanism – an ESR1 mutation is detected.
Importantly, this is an accelerated approval based on PFS, and confirmatory studies are required to verify clinical benefit.
Overall survival data were not yet mature at the time of the primary analysis.
The FDA announcement: FDA Grants Accelerated Approval to Camizestrant With a CDK4/6 Inhibitor for ESR1-Mutated HR-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer․”
You can also read: Beyond CDK4/6: Next-Generation CDK Inhibitors Aim to Overcome Resistance in HR+/HER2− Breast Cancer
