Researchers found that circulating tumor cell counts stratified patients by disease aggressiveness and were associated with differing outcomes following endocrine versus combination therapy.
New clinical trial data support the use of circulating tumor cell (CTC) enumeration to guide treatment decisions in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer whose disease progressed after treatment with aromatase inhibitors plus CDK4/6 inhibitors.
The secondary analysis of the PACE trial, published in Clinical Cancer Research, examined whether CTC count could provide prognostic and predictive information in 203 HR+/HER2- metastatic breast cancer patients progressing after first-line treatment. Patients were randomized to receive either endocrine monotherapy or combination therapy consisting of a doublet or triplet regimen.
Based on CTC levels measured using the Cellsearch system, patients were classified into two prognostic groups: those with fewer than five CTCs per 7.5 mL of blood (indolent disease) and those with five or more CTCs (aggressive disease). While no significant difference in progression-free survival was observed between treatment groups in the overall population, patients with aggressive disease experienced meaningful reductions in progression risk when treated with combination therapies.
The risk of progression was reduced by 57% in patients receiving doublet therapy and 74% in patients receiving triplet therapy, compared with endocrine monotherapy.
“This analysis underscores the value of CTC enumeration to identify HR+/HER2- metastatic breast cancer patients more likely to benefit from intensified therapies after disease progression on first-line treatment,” says Lorenzo Gerratana, MD, associate professor at the University of Udine and physician scientist at IRCCS CRO Aviano (Italy) and lead author of the PACE biomarker analysis, in a release. “Patients with aggressive disease showed improved clinical outcomes with combination therapy, whereas patients with indolent disease did not show a meaningful benefit from treatment escalation compared to monotherapy.”
Consistent with Previous Trial Results
The findings align with results from the STIC trial published in 2024, which showed that treatment decisions guided by CTC counts could differ from physician choice and, when discordant, either led to improved survival outcomes or allowed treatment de-escalation without negatively affecting survival.
CTC count functioned as a standalone predictive biomarker, independent of clinical risk factors and circulating tumor DNA, according to Menarini Silicon Biosystems, which developed the Cellsearch system.
“The STIC and PACE trials consistently demonstrate how our Cellsearch CTC enumeration can improve patient management in the heterogeneous metastatic breast cancer setting, where both resistance mechanisms and disease progression remain a challenge,” says Fabio Piazzalunga, president of Menarini Silicon Biosystems, in a release.
Regulatory Status and Availability
Cellsearch is the only CE-marked, clinically validated blood test cleared by the US Food and Drug Administration for counting CTCs to aid physicians in managing patients with metastatic breast, prostate, and colorectal cancers. The test is available for in vitro diagnostic use in Europe and China, and in the US through the company’s CAP/CLIA/ISO 15189 accredited laboratory in Huntingdon Valley, Pennsylvania.
However, the Cellsearch CTC Kit is not cleared or approved for use to guide specific treatment decisions. The clinical data described involve an investigational use of the Cellsearch system outside its cleared indications and have not been submitted to or reviewed by any regulatory authority for approval.
The multicenter phase II PACE clinical study was initiated in 2017 to address the unmet need for reliable biomarkers to guide treatment decisions following disease progression, as the biological mechanisms driving resistance to CDK4/6 inhibitors are not fully understood.
ID 39534476 © Luchschen | Dreamstime.com
