Can the circulating tumor cell (CTC) count be used as an alternative to the clinical evaluation as the basis for determining the first-line treatment choice (chemotherapy or endocrine therapy) in hormone receptor–positive, ERBB2 (also known as HER2)-negative metastatic breast cancer?
In this randomized clinical trial that allocated 778 patients to a clinician-driven choice arm or a CTC-driven choice arm, the CTC arm was noninferior for progression-free survival.
The CTC count may be a reliable biomarker for choosing between chemotherapy and single-agent endocrine therapy as the first-line treatment in hormone receptor–positive ERBB2-negative metastatic breast cancer.
The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor–positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).
To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.
In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator.
Design, Setting, and Participants
In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count–driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor–positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019.
Main Outcome and Measures
The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio.
Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09).
Conclusions and Relevance
This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor–positive, ERBB2-negative metastatic breast cancer.
ClinicalTrials.gov Identifier: NCT01710605
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Bidard F, Jacot W, Kiavue N, et al. Efficacy of Circulating Tumor Cell Count–Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer: The STIC CTC Randomized Clinical Trial. JAMA Oncol. 2021;7(1):34–41. doi:10.1001/jamaoncol.2020.5660
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