Clinical trialPhase 3Breast cancer

First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer

N Engl J Med · 20253256 patients tested; 315 patients randomised (157 camizestrant, 158 aromatase inhibitor)

Bidard FC, Mayer EL, Park YH, et al. N Engl J Med. 2025. 393:569-580

Study type: Clinical trial
Study name: SERENA-6
Phase: Phase 3
Design: Randomised, double-blind (double-dummy) trial with 1:1 randomisation, guided by ctDNA monitoring every 2 to 3 months
Sample size: 3256 patients tested; 315 patients randomised (157 camizestrant, 158 aromatase inhibitor)
Source: N Engl J Med · 2025
Trial registration: NCT04964934

In plain words

In advanced hormone-positive breast cancer, the tumour can become resistant to hormone-blocking drugs (aromatase inhibitors) by developing a change (mutation) called ESR1. In this study, doctors looked for this mutation with a blood test (ctDNA) every 2 to 3 months, before any growth could be seen on scans. Switching early from the hormone-blocking drug to a new tablet, camizestrant, almost doubled the time the disease was kept under control and also preserved quality of life for longer.

Key results

16.0 vs 9.2 months

Median progression-free survival

HR 0.44 (95% CI 0.31–0.60); P<0.0001; interim analysis, median follow-up 12.6 months

21.0 vs 6.4 months

Median time to deterioration of quality of life

HR 0.54 (95% CI 0.34–0.84)

1.3% vs 1.9%

Discontinuation due to adverse events

Drugs in this study:Abemaciclib (Verzenio)Letrozole (Femara)Palbociclib (Ibrance)Anastrozole (Arimidex)Ribociclib (Kisqali)

Dose and schedule cards

Switch to camizestrant on emergence of an ESR1 mutation (SERENA-6; trial regimen)

Advanced ER-positive/HER2-negative disease after at least 6 months of first-line treatment with an aromatase inhibitor + CDK4/6 inhibitor, with an ESR1 mutation emerging in ctDNA (monitored every 2 to 3 months) without radiologic progressionCycle length: ContinuousOn the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Drug	Dose	Route	Schedule
Camizestrant (in place of the aromatase inhibitor)	75 mg once daily	Oral	Continuous
The same CDK4/6 inhibitor as before	Previous dose	Oral	Continued

Cycle length: Continuous
Duration: Until progression

A new drug; dose from the SERENA-6 trial. Treatment discontinuation due to adverse events was 1.3%.

On the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Camizestrant + continued CDK4/6 inhibitor

Camizestrant 75 mg orally once daily + continuation of the same CDK4/6 inhibitor: palbociclib (125, 100 or 75 mg orally daily, 21 days on and 7 days off), abemaciclib (150, 100 or 50 mg orally twice daily) or ribociclib (orally daily, 21 days on and 7 days off) + aromatase inhibitor placebo. In men and in pre-‎ or perimenopausal women, a monthly LHRH agonist.

2Continued aromatase inhibitor + CDK4/6 inhibitor

Anastrozole 1 mg or letrozole 2.5 mg orally once daily + the same CDK4/6 inhibitor (doses above) + camizestrant placebo.

Source of the regimen details: Abstract of the paper (camizestrant 75 mg daily) and ClinicalTrials.gov NCT04964934 (doses of the aromatase and CDK4/6 inhibitors)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with oestrogen receptor-positive (ER+‎), HER2-negative advanced breast cancer who had received at least 6 months of first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) and in whom an ESR1 mutation emerged on ctDNA monitoring, without radiological disease progression.

Endpoints

Primary outcome: investigator-assessed progression-free survival (PFS).

Secondary outcomes: including time to deterioration of patient-reported quality of life and global health status, PFS2 and overall survival.

Safety and side effects

Discontinuation due to adverse events was low: 1.3% with camizestrant versus 1.9% with an aromatase inhibitor. Full adverse event details (including grade 3 or higher events) are in the full text.

Clinical significance and place in guidelines

In September 2026 the FDA granted accelerated approval to camizestrant (Etcamah, AstraZeneca) with a CDK4/6 inhibitor for HR-positive, HER2-negative advanced breast cancer with an emerging ESR1 mutation detected in ctDNA during treatment with an aromatase inhibitor and a CDK4/6 inhibitor, and accepted the Guardant360 CDx test as the companion diagnostic. This is the first therapeutic approval based on detecting a resistance mutation in ctDNA before radiological progression.

Limitations

The results are based on an interim PFS analysis, and overall survival and PFS2 data were still immature; control-arm patients did not routinely cross over to camizestrant at progression, so it is unclear whether an early ctDNA-guided switch is better than switching at progression; repeated ctDNA monitoring is costly and access to it is limited; funded by the manufacturer.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.