Abstract P6-07-16: Evaluation of circulating tumor cell as a marker of prognosis and efficacy in a randomized phase III study in HER2 negative metastatic breast cancer patients treated with capecitabine and docetaxel: JO21095 study
Authors: Masuda N , Yamamoto D , Sato N , Sagara Y , Yamamoto Y , Saito M , Iwata H , Oura S , Watanabe J , Kuroi K 
Published: August 2014

Abstract
Introduction: Circulating tumor cell (CTC) has been reported as a predictive marker of prognosis and treatment response in metastatic breast cancer by comparing CTC count prior to and after treatment. However, most of previous reports were based on retrospective studies and still controversial. We prospectively evaluated CTC as a marker of prognosis and treatment efficacy in a randomized multi-center phase III study in HER2 negative metastatic breast cancer patients (pts) in Japan.
Methods: Pts were randomized into two groups to receive either the concurrent therapy of capecitabine plus docetaxel in 3-week cycle (XT group) or the sequential therapy of docetaxel followed by capecitabine at progression of disease in 3-week cycle (T→X group). Primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR) and safety. The number of CTC in 7.5 mL of blood sample was measured at the time of screening, after cycle 1, after cycle 2 and at progression of disease (PD) in both groups. Measurement of CTC was conducted by CellSearch System of Veridex. Our evaluation on CTC count was conducted in the XT group and the docetaxel phase of the T→X group.
Results: Of the total 163 pts enrolled in the study, CTC count was evaluated in 158 pts. The number of pts with &lt;2 CTCs was 88 (55.7%) and ≥2 CTCs were 70 (44.3%) at screening. The CTC count was higher in patients with liver or bone metastasis. In pts with ≥2 CTCs, liver metastasis was reported in 47 pts (64%) and bone metastasis in 53 pts (64%) while metastases were less in pts with &lt;2 CTCs. Between the XT group and the docetaxel phase of the T→X group, the median PFS was 10.5 months and 9.8 months (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40–0.97) and ORR was 70% and 61%. Analysis of the OS data is under examination. Subgroup analysis showed PFS was longer in pts with liver metastasis (HR = 0.39; 95% CI = 0.19–0.84) or lung metastasis (HR = 0.43; 95% CI, 0.21–0.90) in the XT group. As a result of our exploratory analysis on CTC count, the median PFS was 10.7 months in pts with &lt;2 CTCs and 8.2 months in pts with ≥2 CTCs (HR, 0.65; 95% CI, 0.42–0.99) at screening. The median PFS of pts with ≥2 CTCs at screening and decreased to &lt;2 CTCs after receiving one cycle of study treatment was 8.3 months and that of pts remained ≥2 CTCs was 8.2 months (HR, 0.79; 95% CI, 0.43–1.46). Between the XT group and the T→X group, the respective median PFS was 10.7 months and 12.1 months (HR, 0.83; 95% CI, 0.46–1.49) in pts with &lt;2 CTCs while it was 10.4 months and 7.1 months in patients with ≥2 CTCs (HR, 0.53; 95% CI, 0.28–0.99). No major safety issues of concern were reported.
Conclusion: Results from our study suggested the CTC count at screening could serve as a marker of prognosis and during treatment as a marker of treatment efficacy. The median PFS in the XT group was longer than the T→X group in pts with liver metastasis or ≥2 CTCs. Aggressive treatment with the concurrent therapy of capecitabine and docetaxel could be a preferable treatment option for HER2 negative metastatic breast cancer patients with ≥2 CTCs in the future.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-16.