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Increased CTCs after chemotherapy associated with worse prognosis in metastatic breast cancer
Patients with metastatic breast cancer who had persistently increased levels of circulating tumor cells between baseline and 21 days after first-line chemotherapy demonstrated shorter OS than patients whose counts declined after treatment, according to study results.
An early switch to another cytotoxic regimen failed to prolong survival among those with increased circulating tumor cells (CTCs), researchers added.
Jeffrey B. Smerage, MD, PhD, clinical associate professor of medical oncology at University of Michigan Comprehensive Cancer Center, and colleagues evaluated data from 595 patients with metastatic breast cancer.
At baseline, 276 patients (46%) did not have increased CTCs — defined as five or more CTCs per 7.5 mL of whole blood — and remained on initial therapy until disease progression.
The other 319 patients had elevated CTCS at baseline. Of them, 165 demonstrated reduced CTC counts after 21 days of therapy and 123 patients continued to show persistently increased levels. Thirty-one patients (10%) were not re-tested following therapy.
Smerage and colleagues assigned the 123 patients with increased CTCs after 21 days of therapy to switch therapies (n=59) or continue initial therapy (n=64).
Overall, researchers reported median OS of 13 months among patients who had increased CTCs after therapy. That was significantly shorter than the median OS observed among patients who did not have increased CTCs at baseline (35 months) and those whose CTC counts improved after therapy (23 months; P<.001).
Cox analyses, adjusted for HR and HER-2 status, indicated CTCs were significantly associated with OS in each of the cohorts (P˂.001).
When researchers analyzed patients who had persistently increased CTC levels after initial treatment, they observed similar median OS among those who switched to another regimen and those who continued their initial therapy (12.5 months vs. 10.7 months; P=.98).
“These data demonstrate that failure of treatment to reduce CTCs within the first 3 to 4 weeks of starting first-line chemotherapy in patients with metastatic breast cancer portends a poor prognosis,” Smerage and colleagues concluded. “Indeed, this circumstance is indicative of general chemotherapy resistance, and early switching to an alternative chemotherapeutic regimen is of no value. We propose that patients who are found to have increased CTCs after one cycle of chemotherapy should strongly consider participating in trials of novel therapeutic agents at the time of progression rather than moving on to second or later lines of chemotherapy.”
Disclosure: The researchers report employment/leadership positions with, consultant/advisory roles with, and research funding or honoraria from Amgen, Immunicon, Janssen Diagnostics, Novartis, Roche/Genentech and Veridex.