Clinical activity of camizestrant, a next-generation SERD, versus fulvestrant in patients with a detectable ESR1 mutation: Exploratory analysis of the SERENA-2 phase 2 trial.

• DOI: 10.1200/jco.2023.41.16_suppl.1066
• Publication Date: 2023-06-04T14:10:33Z
• Authors: Mafalda Oliveira; Denys Pominchuk; Erika P. Hamilton; Yaroslav Kulyaba; Tamar Melkadze; Patrick Neven; Gia Nemsadze; Timur Andabekov; Yuriy Semegen; Yevhen Hotko; Claudio Zamagni; Vladimir Vladimirov; Maxine Bennett; Carmela Ciardullo; Teresa Klinowska; Justin P O Lindemann; Robert McEwen; Christopher J. Mo...; Ekaterine Arkania
• Keywords: Fulvestrant; Progression-free survival; Post-hoc analysis

1066 Background: Camizestrant, a next-generation oral selective estrogen receptor antagonist and degrader (ngSERD), was compared at two dose levels to fulvestrant 500 mg (F) in post-menopausal women with advanced ER+, HER2˗ breast cancer disease recurrence or progression after ≤1 endocrine therapy the setting Phase 2 randomized SERENA-2 study (NCT04214288). Camizestrant demonstrated statistically significant clinically meaningful benefit vs F progression-free survival (PFS) overall population (Oliveira M et al. SABCS 2022 Annual Meeting. Abstract GS3-02.). Methods: Baseline circulating tumour DNA collected screening and/or Cycle 1 Day analysed by sequencing. A post hoc exploratory analysis investigator assessed PFS camizestrant (data from 75 150 combined) patients detectable baseline ESR1 (the gene that encodes ERα) hotspot mutations ( ESR1m). Patients were divided into subgroups based on whether >1 ESR1m variants detected, specific ESR1m, detected BRCA1/2 MAPK pathway. The most prevalent are presented. Cox proportional hazards model used compare PFS. Results: 48/147 (32.7%) treated 35/73 (47.9%) had least sample. 6/9 (67%) mutation 5/26 (19%) pathway alteration; however, numbers too small analyse efficacy these subgroups. Conclusions: showed improved outcome tested. greatest median improvement seen where single variant suggesting early intervention upon detection of an may provide maximum patient for camizestrant, hypothesis is being tested SERENA-6 clinical trial (NCT04964934). Clinical information: NCT04214288 . [Table: see text]