According to results of the Phase III SWOG S0500 clinical trial, switching chemotherapy based on level of elevated CTCs after one cycle of chemotherapy did not improve OS or PFS in women with metastatic breast cancer.
Photo Courtesy © SABCS/Todd Buchanan 2013
Jeffrey B. Smerage, MD, PhD
According to results of the Phase III SWOG S0500 clinical trial presented at the 2013 San Antonio Breast Cancer Symposium, switching chemotherapy based on level of elevated circulating tumor cells (CTCs) after one cycle of chemotherapy did not improve overall survival (OS) or progression-free survival (PFS) in women with metastatic breast cancer.
However, the investigators did validate that the number of CTCs at baseline and 21 days after initiating chemotherapy is highly prognostic in the setting of metastatic breast cancer. Low baseline levels (<5 CTCs/7.5 mL) signaled a very good prognosis, with median OS of 35 months in this trial. Elevated CTCs at baseline that drop below the threshold after one cycle of chemotherapy were associated with median OS of 23 months. Patients with elevated CTCs after one cycle of chemotherapy had the worst prognosis, with median OS of 13 months.
“Although chemotherapy may be effective in some patients [with elevated CTCs], it does not work as long as one would like. This suggests that this patient population needs more effective treatment options beyond traditional chemotherapy,” noted lead study author Jeffrey B. Smerage, MD, PhD, clinical associate professor at the University of Michigan Comprehensive Cancer Center in Ann Arbor. “Given that these patients have higher cancer-related risks, early consideration of clinical trial participation would be appropriate.”
SWOG S0500 recruited 624 patients between 2006 and 2012 who were starting first-line chemotherapy for evaluable metastatic disease that included bone metastases. Of 595 enrollees deemed eligible for the trial, the 276 patients who had low CTCs at baseline were assigned to the observation cohort (Arm A) and monitored for PFS and OS; 319 patients had elevated CTCs at baseline, 10% of whom (n = 33) could not complete follow-up CTC evaluation because of death, progression, or refusal.
At day 21 after the first chemotherapy dose, the remaining 286 patients who had elevated baseline CTC levels had their CTCs drawn again: 163 of these patients were found to have decreased levels of CTCs and assigned to continue their initial chemotherapy (Arm B). The 123 patients with elevated CTCs at day 21 were randomized to continue their initial chemotherapy (Arm C1; n = 64) or were randomized to Arm C2 and had a switch in chemotherapy (n = 59 patients).
Median OS was the same for both the maintain-therapy arm and the switch-therapy arm (12 months); median PFS was 3.5 months for Arm C1 and 4.6 months for the Arm C2, which was not statistically significant.
“CTCs are not a good marker in helping to decide when to switch between chemotherapies,” said Smerage. “Our hope was that switching would both increase the chances of having an effective therapy and decrease exposure to toxicity from less effective therapies, and that early switching based on CTCs would improve survival and time to progression.”
Future studies will analyze CTCs on a molecular level, which should provide predictive information beyond that of just counting the number of cells, Smerage noted.
Smerage JB, Barlow WE, Hayes DF, et al. SWOG S0500A randomized phase III trial to test the strategy of changing therapy versus maintaining therapy for metastatic breast cancer patients who have elevated circulating tumor cell (CTC) levels at first follow-up assessment. Presented at: the 36th Annual San Antonio Breast Cancer Symposium held December 10-14, 2013, San Antonio, TX. Abstract S5-07.