Circulating tumor cells as a prognostic marker for efficacy in the randomized phase III JO21095 trial in Japanese patients with HER2-negative metastatic breast cancer
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Prognostic effects of circulating tumor cells (CTCs) have been reported in metastatic breast cancer (MBC). However, few phase III trials have investigated the potential role of CTCs in treatment selection. We explored potential relationships between CTCs, efficacy, and differential treatment effects.
Patients with HER2-negative MBC were randomized to receive either concurrent capecitabine plus docetaxel (XT) or sequential single-agent docetaxel followed by single-agent capecitabine at progression (T → X). Blood samples were collected at baseline, on day 1 of cycles 2 and 3, and at progression. CTCs were counted using the CellSearch® System. The relationship between baseline CTC count and outcomes was investigated using a pre-defined threshold of 2 CTCs/7.5 mL.
At screening, 44% of the 148 enrolled patients had positive CTC score. In multivariate analyses of pooled treatment arms, positive baseline CTC and triple-negative disease were strongly associated with worse progression-free survival (PFS) and overall survival (OS). Patients with positive CTC score at the baseline had worse OS, irrespective of change in CTC (decreased versus remaining positive) at cycle 2. The prognostic effect of baseline CTC count on OS appeared slightly less pronounced in XT-treated pts. compared with T → X.
A baseline CTC count ≥2 CTCs/7.5 mL was associated with worse prognosis. However, some improvement in PFS and OS was shown with concurrent XT, thus baseline CTC could be a predictive marker. As the current trial was not designed to evaluate a change in chemotherapy according to on-treatment CTC changes, prospective investigation is required.
KeywordsCirculating tumor cells Prognostic factor HER2-negative Metastatic breast cancer Phase III trial
The authors wish to thank the patients and their families, the study site personnel, and the study team for their participation in the trial. The JO21095 study was sponsored by Chugai Pharmaceutical. Chugai Pharmaceutical was involved in study design, statistical analyses, and data interpretation. Chugai Clinical Research Center Co., Ltd. gathered and managed data, and EPS Corporation Co., Ltd. was responsible for data monitoring. The principal investigators had full access to all study data and had final responsibility for approval and submission of the manuscript.
Compliance with ethical standards
Conflict of interest
H Iwata has received honoraria from Chugai Pharmaceutical and has served as a consultant or advisory role for Chugai Pharmaceutical; N. Masuda has received honoraria from Chugai Pharmaceutical, Astra-Zeneca, and Kyowa Hakko Kirin; S. Hattori has served as a consultant or advisory role for Chugai Pharmaceutical; D. Yamamoto, Y. Sagara, N. Sato, Y. Yamamoto, M. Saito, T. Fujita, S. Oura, J. Watanabe, M. Tsukabe, K Horiguchi, Y. Matsuura, and K. Kuroi declare that they have no conflict of interest.
The ethical committee approved the study protocol and all patients provided written informed consent before entering the study.
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