ECLECTIC: 18F-fluoroestradiol PET and circulating biomarkers to guide the choice of the second line therapy for ER+, HER2- metastatic breast cancer: A phase 3 trial.

person Francois Clement Bidard Institut Curie, Paris and Saint Cloud, France info_outline Francois Clement Bidard, Audrey Bellesoeur, Nawale Hajjaji, Elise Rowinski, Alexandre De nonneville, Marie Alexandre, Paul Lalire, Antoine Deleuze, Catherine Alix-Panabières, Isabelle Turbiez, Frederique Berger, Romain-David Seban

Authors person Francois Clement Bidard Institut Curie, Paris and Saint Cloud, France info_outline Francois Clement Bidard, Audrey Bellesoeur, Nawale Hajjaji, Elise Rowinski, Alexandre De nonneville, Marie Alexandre, Paul Lalire, Antoine Deleuze, Catherine Alix-Panabières, Isabelle Turbiez, Frederique Berger, Romain-David Seban Organizations Institut Curie, Paris and Saint Cloud, France, Institut Curie, Paris, France, Centre Oscar Lambret, Lille, France, Centre Léon Bérard, Lyon, France, Institut Paoli Calmette, Marseille, France, Institut du Cancer de Montpellier, Montpellier, France, Institut de Cancerologie de l'Ouest, Saint Herblain, France, Centre Eugène Marquis, Rennes, France, CHU Saint Eloi, Montpellier, France, Institut Curie, Saint Cloud, France Abstract Disclosures Research Funding GE Healthcare Institut Curie Background: In estrogen receptor positive (ER+), HER2-, metastatic breast cancer (mBC) patients, the use of CDK4/6i has considerably extended first-line PFS but also shortened PFS achieved by subsequent endocrine therapies (ET). Contemporary trials demonstrated that a core population of patients (~25-40% of patients) experienced a sustained benefit from second line ET (1,2). Customizing the treatment selection between ET and chemotherapy (given as immediate post-CDK4/6i second line therapy) is therefore of paramount importance. 18F-FES PET/CT (EstroTEP) is FDA-cleared and allows a real-time and minimally invasive assessment of ER expression and heterogeneity in metastatic deposits throughout the whole body (3) and therefore stands as a predictive marker for second line ET. In addition, the FDA-cleared circulating tumor cell (CTC) count (CellSearch) is a prognostic marker that has demonstrated its clinical utility, in terms of overall survival, to guide the choice between chemotherapy and single agent ET (4). In this post-CDK4/6i setting, the aim of the ECLECTIC trial is to demonstrate that the use of 18F-FES PET/CT scan and CTC count can distinguish patients who would benefit from chemotherapy from those experiencing a sustained benefit from second line ET. Methods: ECLECTIC is a multicenter pragmatic phase 3 trial promoted by Institut Curie (Paris, France). Main eligibility criteria include ER+, HER2-, mBC, progression after at least 6 months on a first line AI+CDK4/6i regimen, no visceral crisis, patient considered as eligible to second line ET per investigator opinion, informed written consent. At baseline, all patients will undergo 18F-FES-PET/CT (which will be centrally analyzed and compared to 18F-FDG-PET/CT) and CTC count (determined centrally). Circulating tumor DNA will also be collected. Patients with low FES uptake and/or high CTC count will be randomized between receiving standard-of-care ET (arm C: standard arm) or chemotherapy (arm B: experimental arm). In each arm, treatment regimen will be left to the investigator choice (combining ET with available targeted therapies is allowed in the standard arm; using ADC, if available, as chemotherapy in the experimental arm is allowed). Patients with both low CTC count and high FES uptake (heterogenous metastatic diseases are allowed if FES-negative metastatic sites are accessible to local therapy, e.g., stereotactic irradiation) will receive standard of care ET in a prospective cohort (Arm A). The primary objective of ECLECTIC is to demonstrate the superiority of chemotherapy (Arm B) over ET (Arm C) in the selected patient population, in terms of PFS. Secondary objectives include the efficacy of ET in patients with very favorable features (Arm A), early changes of circulating biomarker, and overall survival. 1. Bidard, JCO 2022. 2. Turner, NEJM 2023. 3. van Geel, JCO 2022. 4. Bidard, JCO 2023. Clinical trial information: 06195709.