Abstract GS3-09: GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial

Abstract Background: High circulating tumor cell (CTC) count (CTChigh) is a strong adverse prognostic factor in patients with metastatic breast cancer (mBC). In the STIC CTC trial (NCT01710605), run before the introduction of CDK4/6 inhibitors for ER+/HER2- mBC, we showed that CTC count (CTC arm) was non inferior to clinician’s choice (standard arm) on progression-free survival (PFS) to guide first line treatment selection between chemotherapy (CT) and endocrine therapy (ET) (Bidard et al., JAMA Oncol 2021). Of note, patients who had treatment escalated from ET (a priori clinician choice) to CT in the CTC arm, had a significantly longer PFS. We report here overall survival (OS) results of this multicenter CTC clinical utility trial. Methods: In the CTC arm, N=377 patients had their treatment determined by baseline CTC count: CT if CTChigh (≥5 CTCs/7.5 mL, CellSearch®), ET if CTClow. In the standard arm (N=378 patients), the choice was left to the investigator: CT if clinical high risk (Clinhigh), ET if clinical low risk (Clinlow). Therefore, patients with discordant Clinlow/CTChigh or Clinhigh/CTClow profiles had their first line treatment escalated from ET (standard arm) to CT (CTC arm) or de-escalated from CT (standard arm) to ET (CTC arm), respectively. Patients with concordant Clinlow/CTClow and Clinhigh/CTChigh profiles received ET and CT in both arms, respectively. Results: Among 755 randomized patients, N=189 (25.0%) had a Clinlow/CTChigh profile, N=103 (13.6%) Clinhigh/CTClow, N=363 (48.2%) Clinlow/CTClow and N=100 (13.2%) Clinhigh/CTChigh. OS was analyzed after a median follow-up of 57 months and 382 events (50.6%). In the Clinlow/CTChigh subgroup, CT in the CTC arm led a longer OS (mOS: 51.8 months [43.3-NR]) than ET in the standard arm (35.4 months [30.4-45.4]; HR=0.53 [0.36-0.78], p=0.001). In patients Clinhigh/CTClow, no significant difference was observed whether they received CT (standard arm) or ET (CTC arm) (45.9 months [36.3-59.8] vs 49.4 months [35.4-65.4]; HR=0.88 [0.51-1.51], p=0.63). Pooling the two discordant groups (Clinlow/CTChigh or Clinhigh/CTClow), the CTC-driven strategy was superior to the clinician-driven treatment decision (HR=0.63 [0.46-0.86], p=0.02). Pooling all concordant and discordant groups together, a median OS of 45.5 (95%CI=[40.9-51.1]) and 51.3 months [46.8-55.1] was observed in the standard and CTC arms, respectively (HR=0.84 [0.69-1.03], p=0.10). Conclusions: Prognostic information brought by CTC or standard factors is discordant in 40% of patients with ER+ HER2- mBC. In case of a discordant estimate, the STIC CTC trial shows the superiority on OS of the CTC-driven treatment decision strategy. These results also suggest a possible clinical utility of CTC to adjust systemic treatment for mBC in second and later lines, after progression on CDK4/6 inhibitors. Funding:The study was funded by Institut Curie; the French National Cancer Institute (INCa), as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011 (STIC 2011); and Menarini Silicon Biosystems (Castel Maggiore, Italy). Citation Format: Francois-Clement Bidard, Nicolas Kiavue, Catherine Alix-Panabières, Sylvain Dureau, Thomas Bachelot, Hugues Bourgeois, Anthony Gonçalves, Etienne Brain, Sylvain Ladoire, Florence Dalenc, Joseph Gligorov, Luis Teixeira, George Emile, Jean-Marc Ferrero, Delphine Loirat, Luc Cabel, Véronique Diéras, Frédérique Berger, William Jacot, Jean-Yves Pierga. GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-09.