Analysis of the Randomized STIC CTC Trial in ER-Positive/HER2-Negative Metastatic Breast Cancer: Overall Survival Findings

Circulating tumor cell (CTC) count is used as a prognostic factor in patients with metastatic breast cancer. In the multicenter STIC CTC trial (NCT01710605), preceding the approval of CDK4/6 inhibitors for ER-positive/HER2-negative metastatic breast cancer, it was demonstrated that CTC count was noninferior to physicians’ choice on progression-free survival (PFS) to guide first-line therapy selection between endocrine therapy (ET) and chemotherapy (CT); particularly, patients who escalated from ET to CT in the CTC cohort had a significantly longer PFS. Adding to the data previously released, overall survival (OS) results from the STIC CTC trial are reported.

In this study comparing CTC-based treatment decision-making to physicians’ choice, 377 patients had treatment determined by baseline CTC and 378 patients had treatment determined by physicians’ choice. For patients in the CTC cohort, CT was initiated for any patients deemed to have high CTC levels (CTC-high; ≥5 CTCs/7.5 mL, CellSearch®) and ET was initiated for any patients with low CTC levels (CTC-low; <5 CTCs/7.5 mL, CellSearch®). In the “standard” physicians’ choice arm, discretion was left to the investigator: CT for patients with high clinical risk (Clin-high) and ET for low clinical risk (Clin-low). Patients with discordant Clin-low/CTC-high or Clin-high/CTC-low profiles had 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 Clin-low/CTC-low and Clin-high/CTC-high profiles received ET and CT in both arms, respectively.

Among 755 patients, 25% (N = 189) had a Clin-low/CTC-high profile, 13.6% (N = 103) had Clin-high/CTC-low, 48.2% (N = 363) had Clin-low/CTC-low, and 13.2% (N = 100) had a Clin-high/CTC-high profile. OS was analyzed after a median follow-up of 57 months and 382 events (50.6%). In the Clin-low/CTC-high subgroup, CT in the CTC arm was found to elicit longer median OS (mOS; 51.8 months [95% confidence interval (CI), 43.3-not evaluable]) than ET in the standard arm (35.4 months [95% CI, 30.4-45.4]; hazard ratio [HR], 0.53 [95% CI, 0.36-0.78]; P = .001). In patients with the Clin-high/CTC-low profile, no significant difference was observed regardless of receiving CT (standard arm) or ET (CTC arm) (45.9 months [95% CI, 36.3-59.8] vs 49.4 months [95% CI, 35.4-65.4]; HR, 0.88 [95% CI, 0.51-1.51]; P = .63). When pooling the 2 discordant groups (Clin-low/CTC-high or Clin-high/CTC low), CTC-driven therapy was found to be superior to clinician-driven treatment (HR, 0.63 [95% CI, 0.46-0.86]; P = .02). Among pooling all concordant and discordant groups, mOS was revealed to be 45.4 (95% CI, 40.9-51.1) and 51.3 months (95% CI, 46.8-55.1) in the standard and CTC arms, respectively (HR, 0.84 [95% CI, 0.69-1.03]; P = 0.10).

Investigators concluded that prognostic information provided by CTC or standard factors is discordant in 40% of patients with ER-positive/HER2-negative metastatic breast cancer. With discordant estimates, the STIC CTC trial shows superiority on OS of CTC-driven treatment decision-making. These results additionally suggest possible clinical utility of CTC for adjusting systemic treatment in patients with metastatic breast cancer in second and later lines.


Bidard FC, Kiavue N, Alix-Panabières C, et al. Circulating tumor cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial. San Antonio Breast Cancer Symposium 2022. Abstract GS3-09.

Related Items

Conference Correspondent Coverage is Brought to You by the Publishers of:
Journal of Hematology Oncology Pharmacy
Journal of Oncology Navigation & Survivorship

Learn more about our family of publications.

View Our Publications