François-Clément Bidard, MD, PhD: Circulating Tumor Cells May Help Improve Outcomes in Metastatic Disease

The purpose of the STIC CTC study was to interrogate the clinical utility of circulating tumor cell count as a biomarker to drive the treatment decision between endocrine therapy and chemotherapy in ER-positive HER2-negative metastatic breast cancer patients. What we did is we collected, on one hand, the clinicians best estimate whether a patient should be treated with endocrine therapy or chemotherapy, and on the other hand, we also collected a circulating tumor cell count by the CELLSEARCH system. Then, the design of our study is like the MINDACT trial, so patients with concurrent estimates. Patients for whom endocrine therapy was a best treatment option according to physician's choice and also had a low CTC count, these patients were treated with endocrine therapy. On the other side of the spectrum, patients that were to be treated with chemotherapy according to the physician and a high CTC count also received chemotherapy. What is interesting is that we had 40% of patient with discrepant estimates between the clinician estimates and the CTC count. What the overall survival results reported earlier show is we have a benefit in terms of overall survival for the population of patients who were clinical low, which means endocrine therapy was a favorite treatment option according to the physician, and had a CTC-high count. And so these patients were treated with chemotherapy in the experimental arm. That benefit is very clinically meaningful, because the delta, the difference, between the two median overall survival was 16 months. The main limitation of our trial is that the trial was run prior to the use of CDK4/6 inhibitor in first line. I have to be clear here, our results do not apply to CDK4/6 inhibitor naive-patients. For these patients, endocrine therapy plus CDK4/6 inhibitor must remain standard of care and the CTC count has not demonstrated any utility in that setting. However, what is very relevant is that CDK4/6 inhibitors are now moving to the adjuvant setting and we also have patients that are progressing on first-line CDK4/6 inhibitor. We know that for these patients we currently don't know exactly how to propose the best treatment between a first line of chemotherapy and/or a further line of endocrine therapy, and we believe that our results advocate in favor of the use of circulating tumor cell count as one of several biomarkers that could help improving the second-line therapy. In the next year to come, there will be performed changes in the way we treat patients and the second-line setting. For some patients, will have, still, endocrine therapy agents, for other patients who will have chemotherapy or antibody-drug conjugates. We will have to integrate many biomarkers, which could be ESR1 mutation, which could be HER2-low status. The STIC CTC trial advocates in favor of fusing the circulating tumor cell counts. It is not the only biomarker, but it is a strong prognostic biomarker that could help deciding between different treatment options.