# SERENA-6

Source: https://onco.cc/trials/serena-6/  
OnCo record `serena-6` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first trial to change treatment because of a blood test rather than a scan: switching to camizestrant when an ESR1 mutation appeared in the blood delayed progression by seven months.

## Summary

3,256 patients screened by serial ctDNA; 315 with an emergent ESR1 mutation randomised. PFS 16.0 vs 9.2 months (HR 0.44, P<0.0001). OS immature; no crossover. FDA ODAC voted 6-3 against (30 April 2026), questioning the clinical meaning of acting on ctDNA before progression; the FDA nonetheless granted accelerated approval on 4 September 2026 (Etcamah), the first ctDNA-triggered switch indication.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT04964934
- Phase: 3
- Setting: First-line HR+/HER2- advanced breast cancer on AI + CDK4/6 with an ESR1 mutation detected in ctDNA before radiographic progression: switch to camizestrant + CDK4/6 vs continue AI + CDK4/6
- Sponsor: AstraZeneca
- Enrolled: 315
- Result: PFS 16.0 vs 9.2 months, HR 0.44.
- Outcomes: Progression-free survival: Switch to camizestrant + CDK4/6 16 months vs Continue AI + CDK4/6 9.2 months, HR 0.44
- Replication: Single trial; the strategy (ctDNA-triggered switch) has not been replicated with another agent. OS pending.

## Sources

- ClinicalTrials.gov NCT04964934: https://clinicaltrials.gov/study/NCT04964934
- ASCO Post approval: https://ascopost.com/news/september-2026/fda-approves-camizestrant-combination-regimen-for-locally-advanced-or-metastatic-breast-cancer/
- ODAC vote (CancerNetwork): https://www.cancernetwork.com/view/fda-odac-no-camizestrant-for-hr-her2-esr1-advanced-breast-cancer

## Connected records

- collections: [CancerNetwork (ONCOLOGY)](https://onco.cc/collections/src-cancer-network/), [The ASCO Post](https://onco.cc/collections/src-asco-post/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- drugs: [Camizestrant](https://onco.cc/drugs/camizestrant/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [ESR1 mutation](https://onco.cc/terms/esr1-mutation/), [ODAC (Oncologic Drugs Advisory Committee)](https://onco.cc/terms/odac/), [Progressive disease and radiographic progression](https://onco.cc/terms/progressive-disease/), [Selective oestrogen receptor degrader (SERD)](https://onco.cc/terms/serd/)
- people: [Nicholas Turner](https://onco.cc/people/nicholas-turner/)
- key papers: [First-Line Camizestrant for Emerging ESR1 -Mutated Advanced Breast Cancer](https://onco.cc/key-papers/paper-serena-6-n-engl-j-med-2025/)
- pairings: [Oral SERD + CDK4/6 inhibitor after ESR1 emergence](https://onco.cc/pairings/oral-serd-plus-cdk46-after-esr1/)
- ideas: [Molecular-progression switching beyond ESR1](https://onco.cc/ideas/idea-ctdna-switch-generalised/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- roadmaps: [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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JSON: https://onco.cc/api/v1/entities/serena-6.json