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. Morrow, Ekaterine Arkania
Published: 2023-06-04
DOI: 10.1200/jco.2023.41.16_suppl.1066
Source: Full article
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 with disease recurrence or progression after ≤1 endocrine therapy in the advanced setting in the Phase 2 randomized SERENA-2 study (NCT04214288). Camizestrant demonstrated statistically significant and clinically meaningful benefit vs F in progression-free survival (PFS) in the overall study population (Oliveira M et al. SABCS 2022 Annual Meeting. Abstract GS3-02.). Methods: Baseline circulating tumour DNA was collected at screening and/or Cycle 1 Day 1 and analysed by next-generation sequencing. A post hoc exploratory analysis compared investigator assessed PFS with camizestrant (data from 75 and 150 mg combined) vs F in patients with detectable baseline ESR1 (the gene that encodes ERα) hotspot mutations ( ESR1m). Patients were divided into subgroups based on whether 1 or >1 ESR1m variants were detected, the specific ESR1m, and whether mutations were detected in BRCA1/2 or the MAPK pathway. The most prevalent mutations are presented. A Cox proportional hazards model was used to compare PFS. Results: 48/147 (32.7%) patients treated with camizestrant and 35/73 (47.9%) treated with F had a detectable ESR1m in at least 1 baseline sample. ESR1m were detected in 6/9 (67%) patients with a BRCA1/2 mutation and 5/26 (19%) with a MAPK pathway alteration; however, the numbers were too small to analyse efficacy in these subgroups. Conclusions: Camizestrant showed improved outcome vs F in patients with a detectable ESR1m at baseline and in the subgroups tested. The greatest median PFS improvement was seen in patients where a single ESR1m variant was detected, suggesting that early intervention upon detection of an ESR1m may provide the maximum patient benefit for camizestrant, a hypothesis that is being tested in the SERENA-6 clinical trial (NCT04964934). Clinical trial information: NCT04214288 . [Table: see text]