François-Clément Bidard, MD, PhD: Circulating Tumor Cells May Help Improve Outcomes in Metastatic Disease
2022 San Antonio Breast Cancer Symposium
François-Clément Bidard, MD, PhD, of the Institut Curie, discusses overall survival results from the STIC CTC trial. To guide the choice between chemotherapy and endocrine therapy for patients with metastatic, estrogen receptor–positive/HER2-negative breast cancer, researchers compared circulating tumor cell (CTC) count to physician’s choice of treatment. The data suggest that the CTC count resulted in better long-term outcomes (Abstract GS3-09).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
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.
Judy C. Boughey, MD, of Mayo Clinic, talks about why breast-conserving therapy may be a treatment option for some patients with multiple breast lesions. For most patients who present with two or three sites of cancer in one breast, mastectomy is recommended. But results from the ACOSOG Z11102 (Alliance) suggest that for women with multiple ipsilateral breast cancer, breast-conserving surgery with adjuvant radiation therapy and lumpectomy site boosts may be beneficial (Abstract GS4-01).
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, discusses results from the POSITIVE trial, which showed that a temporary interruption of endocrine therapy in women with hormone-responsive breast cancer in order to attempt pregnancy, does not affect short-term disease outcomes. The study found that 74% of women had at least one pregnancy, most (70%) within 2 years. Birth defects were low (2%) and were not clearly associated with treatment exposure. Dr. Partridge explains that these data stress the need to incorporate patient-centered reproductive health care in the treatment and follow-up of young women with breast cancer (Abstract GS4-09).
Lisa A. Carey, MD, and Joannie M. Ivory, MD, MSPH, both of the University of North Carolina at Chapel Hill, discuss the higher frequency and treatment implications of nonluminal A or high-risk tumors in Black and younger women. In this study, PAM50 and 21-gene assays revealed different demographic patterns by race and age (Abstract PD1-08).
Aditya Bardia, MD, MPH, of Massachusetts General Hospital, discusses results from the phase III EMERALD trial, the first study to demonstrate improved progression-free survival vs standard of care in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer with one to two prior lines of endocrine treatment, with or without one line of chemotherapy. This finding applied to all patients in the study, including the subgroup with ESR1 mutations (Abstract GS3-01).
Sara A. Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses phase III findings from the DESTINY-Breast03 study, which showed that second-line treatment with fam-trastuzumab deruxtecan-nxki (T-DXd) led to longer overall survival compared with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Patients treated with T-DXd had a 36% lower risk of death than those treated with T-DM1 (Abstract GS2-02).