Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment.

Abstract

ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

• Authors: Nicholas Turner, Cynthia Huang-Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, Cynthia X Ma, Erica L Mayer, Yeon Hee Park, Steven Fox, Xiaochun Liu, Sasha McClain, Francois-Clement Bidard
• Journal: Future oncology (London, England) (Future Oncol) Vol. 19 Issue 8 Pg. 559-573 (Mar 2023) ISSN: 1744-8301 [Electronic] England
• PMID: 37070653 (Publication Type: Clinical Trial Protocol, Journal Article)

Chemical References

• Aromatase Inhibitors
• AZD9833
• Fulvestrant
• Receptor, ErbB-2
• Receptors, Estrogen
• ESR1 protein, human

Topics

• Female
• Humans
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Aromatase Inhibitors (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Clinical Trials, Phase III as Topic
• Fulvestrant (therapeutic use)
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (genetics, metabolism)
• Receptors, Estrogen (metabolism)