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Circulating tumor cell level after chemotherapy predicts OS
Levels of circulating tumor cells after first-line chemotherapy predicted OS among patients with metastatic breast cancer, but changing treatment based on those levels did not increase survival or minimize toxicity, according to study results.
More than 25% of patients with low circulating tumor cells (CTC) at baseline were still alive 5 years after starting first-line therapy, Jeffrey B. Smerage, MD, PhD, clinical associate professor at the University of Michigan Comprehensive Cancer Center, said during a press conference. By comparison, 75% of patients who still had elevated levels after one cycle of chemotherapy had died after about 18 months.
Jeffrey B. Smerage
“These circulating tumor cells are highly prognostic,” Smerage said. “If you’re low at baseline, the median overall survival is 35 months. If you’re high at baseline but convert to low, [overall survival] is 23 months. If you’re high at both time points, median overall survival is 13 months.”
It is estimated that 75% of patients with metastatic breast cancer have detectable CTC in their blood. About half of patients with metastatic breast cancer have elevated CTC levels — defined as ≥5 CTC/7.5 ml whole blood. Elevated CTC levels in blood predicts poor prognosis and relatively short time to progression.
The SWOG S0500 study included 319 patients with metastatic breast cancer who had elevated CTC at baseline and started first-line cytotoxic chemotherapy.
After 21 days, 123 patients still had elevated CTC. Those patients were randomly assigned to continue with the same first-line treatment (n=64) or change treatment (n=59).
“The concept was that we’d be able to identify these patients early [and] switch them to an alternative therapy,” Smerage said. “That way, they would avoid unnecessary cumulative toxicity from a therapy that’s not working … and also improve the odds that they would be on an effective therapy.”
However, results showed no difference in OS (median, 12 months in both groups) and little difference in PFS between the two arms.
“Changing to an alternative chemotherapy early, after only one cycle of chemotherapy, does not improve OS or PFS for patients with metastatic breast cancer whose CTCs don’t decrease to less than 5 after that single cycle of chemotherapy,” Smerage said. “This population … [is] clearly at higher risk based upon that finding. That might influence treatment choices, including the possibility that participation in clinical and translational trials of novel and maybe even targeted therapies would be appropriate early in this patient population, whereas you might wait longer in patients for whom prognosis is considered better.”
Technology has improved since the initiation of this study, hopefully allowing for further research into molecular profiling of the CTCs, Smerage said.
“Protein expression, RNA expression, looking at genetic mutations in these cells, even PHISH are all possible now in these cells in ways that I hope will lead to better ability to predict the appropriate treatment strategies for these patients that simply counting cells doesn’t seem to do,” Smerage said.
For more information:
Smerage JB. Abstract #S5-07. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
Disclosure: The study was funded by the NCI. Smerage reports no relevant financial disclosures.