SAN ANTONIO—Switching to a second-line chemotherapy regimen after one cycle of first-line therapy does not improve overall survival (OS) or time to progression among women with metastatic breast cancer and elevated peripheral-bloodstream circulating tumor cells (CTCs), according to the prospective randomized phase 3 Southwestern Oncology Group (SWOG) S0500 clinical study presented at the 2013 San Antonio Breast Cancer Symposium.

Despite the disappointing findings, CTCs were found to be “highly prognostic in the setting of metastatic breast cancer,” noted Jeffrey B. Smerage, MD, PhD, clinical associate professor at the University of Michigan’s Comprehensive Cancer Center in Ann Arbor, MI.

“This study confirmed that patients who have low numbers of CTCs before starting chemotherapy have much better survival,” noted Dr. Smerage. “They had a median OS of 35 months, which means that half of these patients lived 3 years or longer, and some substantially longer. On the other hand, patients for whom CTCs remained elevated after one cycle of chemotherapy had substantially worse survival. They had a median overall survival of only 13 months.”

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That indicates that chemotherapy might not be as effective when CTCs remain elevated after the first cycle of treatment, Dr. Smerage said. “This does not mean that chemotherapy has no benefit, but it suggests that the benefit is limited.”

The trial enrolled 593 patients with “measurable or evaluable” metastatic breast cancer including bone metastasis, between 2006 and 2012. Of the 595 participants, 276 had low CTCs at baseline and continued to receive their initial chemotherapy, as “arm A” of the study. The other 317 participants were found to have elevated CTCs (defined as ≥ 5 CTC/7.5 mL whole blood, using the CellSearch® platform) at baseline; 286 of these patients had CTC data available at day 21 of the first cycle of initial chemotherapy, Dr. Smerage reported, and for 163 of them, CTCs decreased to lower levels. These patients continued to receive initial chemotherapy and were designated study-arm B.  

The 123 patients with continued elevated CTCs at day 21 were randomly assigned to one of two “C” arms: C1-assigned patients continued to receive initial chemotherapy (n=64), while C2-assigned patients switched to second-line chemotherapy (n=59).

“Changing to an alternative chemotherapy after one cycle did not improve OS or progression-free survival (PFS),” Dr. Smerage concluded. For OS, the hazard ratio (HR) was 1.01 (12 months vs. 12 months; P = 0.83, not significant), and for PFS, HR was 0.91 (3.5 months C1 vs. 4.6 months C2; P =0.61, not significant).

“This study was based on counting the number of CTCs in blood,” noted Dr. Smerage. “Several groups are now investigating the presence of biological markers such as estrogen receptor, HER2, and others on CTCs. It is hoped that the measurement of these markers may allow for better prediction of what therapies will work best for these patients.”

The study was funded in part by Veridex.


  1. Smerage JB. S5-07. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.