Menarini Silicon Biosystems has announced significant findings from the PACE trial, which confirm the clinical utility of Circulating Tumor Cell (CTC) enumeration in guiding treatment decisions for patients with a specific subtype of metastatic breast cancer. The results were published in the journal Clinical Cancer Research on December 22, 2025, and highlight how CTC counts can influence treatment escalation or de-escalation for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer who have seen disease progression after prior treatments with aromatase inhibitors and CDK4/6 inhibitors.
The secondary analysis of the PACE trial underscores the predictive value of CTC counts in a multicenter phase II clinical study initiated in 2017. The analysis involved 203 patients who were randomized to receive either endocrine monotherapy or combination therapies, which included a doublet (endocrine therapy plus a CDK4/6 inhibitor) or a triplet regimen (endocrine therapy, a CDK4/6 inhibitor, and an immune checkpoint inhibitor).
Based on their CTC levels, patients were classified into two prognostic groups: those with fewer than 5 CTCs per 7.5 mL of blood, labeled as having indolent disease, and those with 5 or more CTCs, categorized as having aggressive disease. While there was no significant difference in progression-free survival between treatment groups in the overall population, patients with aggressive disease demonstrated a substantial reduction in the risk of progression when treated with combination therapies. Specifically, the risk of progression was reduced by 57% for those receiving doublet therapy and by 74% for triplet therapy, compared to those on endocrine monotherapy.
Dr. Lorenzo Gerratana, Associate Professor at the University of Udine and Physician Scientist at IRCCS CRO Aviano in Italy, noted, “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.” He emphasized that patients with aggressive disease showed improved clinical outcomes with combination therapies, while those classified with indolent disease did not experience significant benefits from treatment escalation.
The biological mechanisms behind resistance to CDK4/6 inhibitors remain complex, highlighting the need for reliable biomarkers to guide treatment decisions after disease progression. These findings align with previous results from the STIC trial, which indicated that treatment decisions informed by CTC counts could lead to better survival outcomes or allow for treatment de-escalation without adversely affecting survival.
Fabio Piazzalunga, President of Menarini Silicon Biosystems, stated, “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 present challenges.” He added that the test is available for In Vitro Diagnostic Use in Europe and China, and in the United States through their CAP/CLIA/ISO 15189 accredited laboratory in Huntingdon Valley, Pennsylvania.
The CELLSEARCH system is the only CE-marked, clinically validated blood test cleared by the FDA for counting CTCs to assist physicians in managing patients with metastatic breast, prostate, and colorectal cancers. While it is important to note that the CELLSEARCH CTC Kit is not cleared or approved for specific treatment decisions, the data presented in the PACE trial reflects an investigational use of the system outside its cleared indications.
Menarini Silicon Biosystems, headquartered in Bologna, Italy, with a subsidiary in Huntingdon Valley, Pennsylvania, is part of the Menarini Group, a multinational pharmaceutical, biotechnology, and diagnostics company. The group employs over 17,000 individuals across 140 countries, emphasizing its commitment to advancing healthcare through innovative solutions.
