Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)

Summary

The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation.

Timeline

Start

2021-06-30

Primary completion

2025-06-30

Completion

2028-09-01

Outcome

Met primary endpoint

paper hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P<0.0001 PMID 40454637 ↗

paper had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. PMID 40454637 ↗

release “SERENA-6 Phase III trial showed a highly statistically significant and clinically meaningful 56% reduction in the risk of disease progression or death” astrazeneca.com ↗

release “SERENA-6 met its primary endpoint of PFS at the interim analysis” astrazeneca.com ↗

Publications

• Brufsky A, Park YH, Bidard FC, Mayer EL, Janni W, Ma C, Cristofanilli M, Bianchini G, Iwata H, Fasching PA, Nowecki Z, Pascual J, Chen SC, Moreau L, Ruiz-Borrego M, Shai A, Karadurmus N, Jung KH, Kikawa Y, Baird RD, Habash R, Sugarman R, Fox S, Selvi Miralles M, Huang Bartlett C, Turner N. SERENA-6 visual patient-reported outcomes and safety: camizestrant for emerging ESR1m advanced breast cancer during first-line endocrine-based therapy. Oncologist. 2026 Aug 6;31(9):oyag278. doi: 10.1093/oncolo/oyag278.
• Turner NC, Mayer EL, Park YH, Janni W, Ma C, Cristofanilli M, Bianchini G, Kalinsky K, Iwata H, Chia S, Brufsky AM, Fasching PA, Nowecki Z, Pascual J, Karadurmus N, Gal-Yam E, Chung WP, Im SA, Zambelli A, Dalenc F, Oliveira M, Ishiguro H, Huang CS, Klinowska T, Fox S, Morrow C, Robert L, Huang-Bartlett C, Bidard FC. Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 2026 Aug;27(8):941-958. doi: 10.1016/S1470-2045(26)00287-1. Epub 2026 Jul 13.
• Bidard FC, Mayer EL, Park YH, Janni W, Ma C, Cristofanilli M, Bianchini G, Kalinsky K, Iwata H, Chia S, Fasching PA, Brufsky A, Nowecki Z, Pascual J, Moreau L, Chen SC, Karadurmus N, Gal-Yam EN, Jung KH, Pernas S, McClain S, He W, Klinowska T, Huang-Bartlett C, Turner NC; SERENA-6 Study Group. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. N Engl J Med. 2025 Aug 7;393(6):569-580. doi: 10.1056/NEJMoa2502929. Epub 2025 Jun 1.
• Turner N, Huang-Bartlett C, Kalinsky K, Cristofanilli M, Bianchini G, Chia S, Iwata H, Janni W, Ma CX, Mayer EL, Park YH, Fox S, Liu X, McClain S, Bidard FC. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023 Mar;19(8):559-573. doi: 10.2217/fon-2022-1196. Epub 2023 Apr 18.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Anastrozole	Other / unclassified	1 mg	Oral
Subject	Camizestrant	Other / unclassified	75 mg	Oral
Comparator	Letrozole	Other / unclassified	2.5 mg	Oral
Background	Abemaciclib	Small molecule	50 mg	Oral
Background	Abemaciclib	Small molecule	100 mg	Oral
Background	Abemaciclib	Small molecule	150 mg	Oral
Background	Palbociclib	Small molecule	75 mg	Oral
Background	Palbociclib	Small molecule	100 mg	Oral
Background	Palbociclib	Small molecule	125 mg	Oral
Background	Ribociclib	Small molecule	—	Oral

Indications