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

• Published in: Breast cancer research and treatment 2017-04, Vol.162 (3), p.501-510
• Main Authors: Iwata, Hiroji, Masuda, Norikazu, Yamamoto, Daigo, Sagara, Yoshiaki, Sato, Nobuaki, Yamamoto, Yutaka, Saito, Mitsue, Fujita, Takashi, Oura, Shoji, Watanabe, Junichiro, Tsukabe, Masami, Horiguchi, Kazumi, Hattori, Satoshi, Matsuura, Yoshimasa, Kuroi, Katsumasa
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer metastasis; Cancer research; Cancer therapies; Cell Count; Cells; Clinical Trial; Clinical trials; Clinical Trials, Phase III as Topic; Epidermal growth factor; Female; Humans; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplastic Cells, Circulating - pathology; Oncology; Prognosis; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Survival Analysis; Treatment Outcome
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4138-3

Purpose 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. Methods 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. Results 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. Conclusions 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.