A phase III study by Bidard et al investigated whether circulating tumor cells could help physicians choose between hormone therapy or chemotherapy as front-line therapy for patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer. The researchers concluded that the circulating tumor cell count could be an objective decision-making tool when considering first-line therapy for these patients.
In addition, subgroup analyses showed that in patients with discordant treatment recommendations between the clinician estimate and the circulating tumor cell count, front-line chemotherapy was associated with a significant decrease in the risk of death. The study (Abstract GS3-07) was presented at the 2018 San Antonio Breast Cancer Symposium.
Study Methodology and Results
In this phase III study, the researchers randomly assigned 761 patients to either a clinically driven treatment arm of hormone therapy or chemotherapy as decided by a physician based on clinical factors, or a circulating tumor cell–driven treatment arm. (In the latter patients, hormone therapy was administered if 7.5 mL of blood had less than 5 circulating tumor cells, and chemotherapy was administered if 7.5 mL of blood had 5 or more circulating tumor cells.)
After randomization in the clinically driven arm of the study, 72.6% of the patients received hormone therapy and 27.4% received chemotherapy. In the circulating tumor cell–driven arm, among those likely to receive hormone therapy by clinically driven choice, this treatment option was confirmed by a low circulating tumor cell count in 66.7% of the patients; the remaining 33.3% were switched to chemotherapy based on a high circulating tumor cell count. Among patients likely to receive chemotherapy by clinically driven choice, this treatment option was confirmed by a high circulating tumor cell count in 48.1% of the patients. The remaining 52.9% were switched to hormone therapy based on a low circulating tumor cell count.
The primary endpoint was met with progression-free survival proving noninferior in the circulating tumor cell–driven arm, compared with the clinically driven arm.
Patients whose treatment was escalated to chemotherapy based on their circulating tumor cell count had a significantly longer progression-free survival (median = 10.5 months with hormone therapy in the clinically driven arm in patients with a high circulating tumor cell count vs 15.5 months with chemotherapy in the circulating tumor cell arm) and showed a trend toward longer overall survival—37.1 vs 42 months, respectively. In contrast, patients whose treatment was de-escalated to hormone therapy based on their circulating tumor cell count had nonsignificantly shorter progression-free survival and overall survival compared with patients who received chemotherapy in the clinically driven arm with a low circulating tumor cell count.
An analysis that focused on the two subgroups of 292 patients with discordant treatment recommendations showed that patients treated with front-line chemotherapy had a significantly longer progression-free survival (34% less likely to experience disease progression) and overall survival (35% lower risk of death). Overall survival rates at 24 months were 82.9% in patients treated with chemotherapy (and eventually followed by maintenance hormone therapy) vs 74.7% in patients treated with front-line hormone therapy.
Reducing Mortality Rates
“Circulating tumor cell count has been investigated in thousands of [patients with breast cancer] worldwide over the past decade, and numerous analyses have established that, beyond performance status, circulating tumor cell count is the strongest prognostic marker in [patients with] ER-positive, HER2-negative stage IV breast cancer,” said Francois-Clement Bidard, MD, PhD, Professor of Medical Oncology at the Institut Curie, Saint-Cloud in Paris and the University of Versailles in France, and the lead author of this study, in a statement.
“In our study,” Dr. Bidard continued, “not only have we demonstrated that basing the decision on [circulating tumor cell] count alone does not harm patients in the overall study population, but subgroup analyses show that in the 292 patients with discordant treatment recommendations, front-line chemotherapy was associated with a significant 35% decrease in the risk of death.”
Disclosure: Funding for this study was provided by the French Ministry of Health, Menarini Silicon Biosystems, and Institut Curie. See the study authors’ full disclosures at sabcs.org.
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