SERENA-6
Can ctDNA detection of an emerging ESR1 mutation guide an endocrine switch before radiographic progression?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Biomarker.
315 patients with HR-positive/HER2-negative advanced breast cancer with ESR1 mutation detected in ctDNA during first-line AI plus CDK4/6 inhibitor therapy before radiographic progression.
No radiographic progression at molecular detection; requires serial ctDNA testing and actionable ESR1 mutation.
315 randomised after 3,256 screened randomised/evaluable as reported.
Switch to camizestrant 75 mg daily while continuing the CDK4/6 inhibitor.
Continue aromatase inhibitor plus the same CDK4/6 inhibitor.
Endpoints and results
Primary PFS; time to strategy failure, OS, safety and PROs secondary.
- Median PFS 16.0 vs 9.2 months; HR 0.44 (95% CI 0.31–0.60; p<0.0001).
- Time to deterioration in global health status/QoL 21.0 vs 6.4 months; HR 0.54 (95% CI 0.34–0.84).
- Adverse-event discontinuation 1.3% vs 1.9%.
- US FDA accelerated approval granted 4 Sep 2026 for eligible ESR1-mutated disease detected during AI+CDK4/6 therapy.
Absolute Effect and outcome visualisation
Median PFS
months (median, not fixed-time rate) · Primary PFS analysis. Bars compare reported medians only; they are not fixed-time survival probabilities.
Interpretation: No fixed-time PFS rates reproduced here; NNT not calculated. Never derive NNT from the 6.8-month median difference or HR.
Toxicity, discontinuation and quality of life
Trial-specific harms: Adverse-event discontinuation 1.3% vs 1.9%; continue monitoring for drug-specific and CDK4/6 inhibitor toxicity.
Treatment burden/discontinuation: Serial blood testing and molecular result workflow add access, timing and interpretation burden.
Quality of life: Time to deterioration in global health status/QoL favoured early switching (21.0 vs 6.4 months; HR 0.54).
Subgroups, maturity and limitations
Subgroups: Specific to ESR1-mutated disease emerging during first-line AI+CDK4/6 therapy; not a post-progression trial.
Maturity: PFS established; OS follow-up continues for confirmation of clinical benefit.
Limitations: Regulatory status varies by region; companion diagnostic and serial testing requirements matter.
SERENA-6 supports molecularly triggered early switching before radiographic progression, with PFS/QoL benefit but OS confirmation still pending.
Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT04964934
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.