NEW YORK (Reuters Health) – If the first cycle of chemotherapy fails to lower high circulating tumor cells (CTCs), changing to an alternative chemotherapy does not improve outcomes in women with metastatic breast cancer, according to the SWOG S0500 randomized phase III trial.
“We concluded CTCs are not a good marker in helping to decide when to switch between chemotherapies,” said Dr. Jeffrey B. Smerage of the University of Michigan Comprehensive Cancer Center in Ann Arbor, in a statement from the San Antonio Breast Cancer Symposium where he presented the study results December 13.
“It had been hoped that switching would both increase the chances of being on an effective therapy and decrease the exposure to toxicity from less effective or ineffective therapies, and as a result it had been hoped that this early switching would result in improved survival and time to progression,” Dr. Smerage explained. But that didn’t pan out.
About three quarters of women with metastatic breast cancer have detectable CTCs. In about half of these women, the number of CTCs is elevated (> 5 per 7.5 ml whole blood). Elevated CTCs at baseline are associated with a poor prognosis, and a decline in CTCs suggest response to therapy.
The SWOG S0500 trialists recruited women with metastatic breast cancer between 2006 and 2012. Of the 595 women who were eligible for the trial, 276 had low CTCs (< 5) at baseline, and were observed in arm A. These patients continued to receive the initial chemotherapy.
The remaining 319 patients had elevated CTCs at baseline, and 286 had a CTC result available after the first cycle of chemotherapy. In this group, CTCs had fallen in 163 women. They continued with their initial chemotherapy and were observed in study arm B.
Among the 123 patients who continued to have elevated CTCs after the first cycle of chemotherapy, 64 stuck with it (study arm C1) and 59 had their chemotherapy changed to a second-line regimen (study arm C2).
Changing chemotherapy did not improve overall survival, the primary endpoint of the study.
During follow up, 54 of 64 women in arm C1 who continued on first-line therapy died, as did 48 of 59 women in arm C2 who changed therapy. Median overall survival was 12 months in both arms (hazard ratio 1.01). There was also no difference in progression-free survival: 3.5 months in arm C1 and 4.6 months in C2 (HR 0.91).
Dr. Smerage said the study also confirmed that patients with low numbers of CTCs before starting chemotherapy have better survival (median OS 35 months) than patients with elevated CTCs at baseline (median OS 23 months in arm B and 13 months in arm C1/C2).
Patients whose CTCs don’t fall to less than 5 per 7.5 ml blood after one cycle of first line chemotherapy have a “relatively short overall survival,” he told a media briefing.
“It’s important to note,” he added, “that this study was not designed to detect a benefit of chemotherapy so it would not be a correct assumption to say that these patients derive no benefit from chemotherapy; we actually can’t conclude that from the design of this particular study.”
However, when CTCs don’t fall, participation in clinical and translational trials of novel, targeted therapies may be a preferable strategy, Dr. Smerage said.
The study was funded by the National Cancer Institute and in part by Veridex, which manufactures the Cellsearch Circulating Tumor Cell Kit. Dr. Smerage has no conflicts of interest.