First-line doublet chemotherapy for metastatic triple-negative breast cancer: Circulating tumor cell analysis of the tnAcity trial

Minetta C. Liu, Wolfgang Janni, Vassilis Georgoulias, Denise A. Yardley, Nadia Harbeck, Xin Wei, Desmond McGovern, Robert Beck

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10427-10433
Number of pages7
JournalCancer Management and Research
Volume11
DOIs
StatePublished - 2019

Keywords

  • Chemotherapy
  • Circulating tumor cells
  • Metastatic triple-negative breast cancer
  • Nab-paclitaxel
  • Prognosis

ASJC Scopus subject areas

  • Oncology

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