SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.
In the phase 3, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported , from Institut Curie in St. Cloud, France.
“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.
The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.
Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.
The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.
At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.
The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).
Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.
However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.
In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).
, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”
She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.
“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.
The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.
, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.
“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.
The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.
SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.