CTC Count May Help Providers Choose Optimal Therapy for Patients with Metastatic Breast Cancer

TON - February 2023 Vol 16, No 1

Using circulating tumor cell (CTC) count to guide the choice of first-line treatment—chemotherapy or endocrine therapy—improved overall survival (OS) compared with investigator’s choice of treatment for patients with metastatic, estrogen receptor (ER)-positive, HER2-negative breast cancer, according to results from the STIC CTC trial, which were discussed at the 2022 San Antonio Breast Cancer Symposium (SABCS) by François-Clément Bidard, MD, PhD, Co-Coordinator, Breast Cancer Research, Institut Curie, Paris, France, and Professor, Medicine, Department of Medical Oncology, Institut Curie and Université de Versailles Saint-Quentin-en-Yvelines, France.

Among a subgroup of patients representing 25% of the study population, for whom endocrine therapy was the recommended treatment by investigator’s choice but who displayed high CTC count, those who were treated with chemotherapy had an absolute gain of 16 months in median OS and experienced a 47% reduction in risk for death compared with patients in the same group who received endocrine therapy. In this clinically low risk/CTC high group, median OS was 51.8 months in patients treated with chemotherapy compared with 35.4 months in those treated with endocrine therapy (P = .001).

In patients who were deemed clinically high risk but had a low CTC count, who represented 14% of the study population, no significant difference was observed in progression-free survival (PFS) or OS whether patients received chemotherapy or endocrine therapy. In this group, median PFS was 9.3 months in the CTC count–based arm, for whom endocrine therapy is recommended according to guidelines, versus 14.6 months in the standard arm, for whom chemotherapy was selected (P = .54). Median OS was 49.4 months versus 45.9 months (P = .64), respectively.

Study Details

In the STIC CTC trial, 755 patients were randomly assigned in a 1:1 ratio to having their treatment decided by the investigator or by their CTC count. The primary results of this study, which were reported at SABCS in 2018, showed a PFS benefit in patients whose treatment was escalated from endocrine therapy to chemotherapy based on their CTC count.

Guidelines recommend prioritizing endocrine therapy before switching to chemotherapy in patients with metastatic breast cancer, a recommendation based on the favorable side-effect profile of endocrine therapy. Guidelines, however, provide an option to use chemotherapy in patients with aggressive disease, “which has led to highly heterogeneous treatment decisions,” noted Dr Bidard.

“STIC CTC is the first trial to demonstrate the clinical utility of CTC count in metastatic breast cancer,” he said. “The CTC count confirmed the allocated therapy in about 60% of patients and changed the allocated therapy in approximately 40% of ER-positive, HER2-negative patients.”

The study was designed before CDK4/6 inhibitors became the standard of care, admitted Dr Bidard, thus limiting the clinical utility of the findings. In agreement with this point was discussant Daniel F. Hayes, MD, FASCO, FACP, Stuart B. Padnos Professor of Breast Cancer Research, and Professor, Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor.

“It’s not clear to me that this is sufficient for clinical utility in context of what we know today,” he said, citing the availability of modern treatments that did not exist when the study was designed. “There was no ancillary treatment with endocrine therapy, CDK 4/6 inhibitors everolimus [Afinitor], alpelisib [Piqray], oral SERDS [selective estrogen receptor degraders], or AKT inhibitors,” he added.

The study was important in that it confirmed that patients with a clinically high risk/low CTC profile could avoid chemotherapy, although this was only a small percentage of patients enrolled, Dr Hayes noted. “It’s inefficient because the CTCs didn’t really help the way you would treat patients,” he said.

To date, payers have not reimbursed for the use of CTC measurement, questioning its clinical utility, “I don’t think the world of CTCs is dead,” Dr Hayes said. “I think they’re part of liquid biopsies. We should continue them as a complement to [circulating tumor] DNA.”

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