First-Line Doublet Chemotherapy for Metastatic Triple-Negative Breast Cancer: Circulating Tumor Cell Analysis of the tnAcity Trial
Received 2 April 2019
Accepted for publication 14 November 2019
Published 12 December 2019 Volume 2019:11 Pages 10427—10433
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Nakshatri
Minetta C Liu,1 Wolfgang Janni,2 Vassilis Georgoulias,3 Denise A Yardley,4 Nadia Harbeck,5 Xin Wei,6 Desmond McGovern,7 Robert Beck7
1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; 2Department of Obstetrics and Gynecology, University Clinic Ulm, Ulm, Germany; 3Department of Medical Oncology, School of Medicine, University of Crete, Crete, Greece; 4Department of Medical Oncology, Breast Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN, USA; 5Department of Breast Center, Oncological Therapy and Clinical Trials Unit, University of Munich (LMU), Munich, Germany; 6Department of Translational/Clinical Development, Celgene Corporation, Summit, NJ, USA; 7Department of Clinical Research, Celgene Corporation, Summit, NJ, USA
Correspondence: Minetta C Liu
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Tel +1 507 293 0526
Purpose: Circulating tumor cells (CTCs) are prognostic biomarkers in metastatic breast cancer, but their role in predicting treatment outcomes in metastatic triple-negative breast cancer (mTNBC) is less clear. The tnAcity trial demonstrated a significant progression-free survival (PFS) benefit with nab-paclitaxel (nab-P)/carboplatin (C) over nab-P/gemcitabine (G) or G/C in patients with mTNBC. We assessed the correlation between CTC dynamics and clinical benefit in all patients and by treatment arm.
Methods: CTC enumeration, performed using CELLSEARCH technology (Menarini Silicon Biosystems, Huntingdon Valley, PA, USA), was a prespecified exploratory endpoint in the tnAcity trial. Patients with TNBC were categorized based on pre- and post-treatment CTC levels: Group 1 (+ + +; elevated CTCs at baseline and postbaseline), Group 2 (+ ± ±; CTCs elevated at baseline and cleared postbaseline [cycle 3 and/or cycle 5]), or Group 3 (−; no CTCs detected at baseline). The baseline cutoff was ≥1 CTC/7.5 mL for the main analysis; cutoffs of ≥2 and ≥5 CTCs were used for supporting analyses.
Results: The main analysis included 126 patients (Group 1, n = 24; Group 2, n = 54; and Group 3, n = 48). The median PFS was longer in Group 2 vs Group 1 (8.5 vs 4.7 months; HR, 0.30 [95% CI, 0.17–0.54]). These results were supported by the ≥2- and ≥5-CTC cutoff analyses. The median overall survival rates were 17.8, 16.0, and 9.8 months in Groups 2, 3, and 1, respectively. The overall response rates were 79.6%, 43.8%, and 29.2%, respectively. A numerically higher percentage of patients had CTC clearance during nab-P/C treatment vs nab-P/G or G/C.
Conclusion: Efficacy outcomes trended positively with chemotherapy-induced elimination of CTCs, suggesting that CTC clearance may predict the chemosensitivity of mTNBC tumors.
Trial registration: EudraCT Number: 2013-000113-20; ClinicalTrials.gov number: NCT01881230.
Keywords: metastatic triple-negative breast cancer, circulating tumor cells, nab-paclitaxel, chemotherapy, prognosis
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