In the French phase III STIC CTC trial reported in JAMA Oncology, François-Clément Bidard, MD, PhD, and colleagues found that choice of first-line chemotherapy vs endocrine therapy in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer based on circulating tumor cell count resulted in noninferior progression-free survival vs clinician choice.
In the multicenter trial, 755 pre- or postmenopausal women (per-protocol population) were randomly assigned between February 2012 and July 2016 to a circulating tumor cell–driven group (n = 377), in which patients received chemotherapy for circulating tumor cell counts of ≥ 5/7.5 mL (CTC-high) and endocrine therapy for counts < 5/7.5 mL (CTC-low) or a clinician choice group (standard group, n = 378), in which patients received chemotherapy or endocrine therapy based on clinician assessment of high or low risk (clinical-high, clinical-low). The primary endpoint was progression-free survival after 2 years, with a noninferiority margin of 1.25 for the 90% confidence interval (CI) of the hazard ratio (HR).
"This randomized clinical trial found that the circulating tumor cell 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, HER2-negative metastatic breast cancer."— François-Clément Bidard, MD, PhD, and colleagues
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Overall, 37% of the circulating tumor cell group vs 27% of the standard group received chemotherapy. Median progression-free survival was 15.5 months (95% CI = 12.7–17.3 months) in the circulating tumor cell group vs 13.9 months (95% CI = 12.2–16.3 months) in the standard group; the hazard ratio was 0.94, with a 90% confidence interval of 0.81–1.09, which met the noninferiority criterion. Median overall survival was 47.3 months vs 42.8 months (HR = 0.91, 95% CI, 0.71–1.16).
Analyses according to concordant and discordant circulating tumor cell and clinician-assessed status showed median progression-free survival for the circulating tumor cell vs standard groups of 17.3 vs 18.8 months (HR = 1.03, 95% CI = 0.81–1.31) in the clinical-low/circulating tumor cell–low subgroup, 11.3 vs 11.0 months (HR = 0.90, 95% CI = 0.60–1.36) in the clinical-high/circulating tumor cell–high subgroup, 8.1 vs 14.1 months (HR = 1.20, 95% CI = 0.79–1.84) in the clinical-high/circulating tumor cell–low subgroup, and 15.6 vs 10.0 months (HR = 0.62, 95% CI = 0.45–0.84) in the clinical-low/circulating tumor cell–high subgroup.
The incidence of grade 3 or 4 adverse events was low in both groups. The incidence of chemotherapy-related adverse events of any grade was higher in the circulating tumor cell group, including anemia (20.4% vs 14.6%), alopecia (15.1% vs 10.6%), and vomiting (8.2% vs 4.8%).
The investigators concluded, “This randomized clinical trial found that the circulating tumor cell 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, HER2-negative metastatic breast cancer.”
Dr. Bidard, of the Department of Medical Oncology, Institut Curie, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Institut Curie, French National Cancer Institute, and Menarini Silicon Biosystems. For full disclosures of the study authors, visit jamanetwork.com.