#Italy #Bologna #Breast Cancer #Menarini #CTC enumeration

Key Findings from the PACE Trial

Menarini Silicon Biosystems recently published groundbreaking results from the PACE trial in the journal Clinical Cancer Research. This study explored the role of circulating tumor cells (CTCs) in blood for metastatic breast cancer patients, specifically those with hormone receptor-positive (HR+) and HER2-negative (HER2-) subtypes, who have shown disease progression after initial treatment with aromatase inhibitors combined with CDK4/6 inhibitors.

The Importance of CTCs

The secondary analysis of the PACE trial underscored the potential of CTC counting as a predictive biomarker that operates independently of clinical risk factors and circulating tumor DNA. By understanding the levels of CTCs, oncologists can tailor their treatment strategies, deciding whether to intensify or decrease therapy based on individual patient conditions.

Trial Design and Patient Results

Conducted as a multicentric phase II clinical trial initiated in 2017, the PACE analysis involved randomly assigning 203 participants to receive either endocrine monotherapy or a combination therapy approach. The latter included dual therapy (endocrine treatment plus a CDK4/6 inhibitor) or triple therapy (endocrine treatment plus a CDK4/6 inhibitor and an immune checkpoint inhibitor). Patients were categorized into two prognostic groups based on their CTC counts: those with fewer than 5 CTCs per 7.5ml of blood (considered as having indolent disease) and those with 5 or more CTCs (categorized as having aggressive disease).

Interestingly, while no significant differences in progression-free survival were observed across treatment groups in the broader population, patients with aggressive disease benefitted substantively from combination therapies. Specifically, those treated with double therapy experienced a 57% reduction in progression risk, while those on a triple regimen enjoyed an impressive 74% reduction, in contrast to those receiving monotherapy.

Clinical Implications and Expert Insights

Dr. Lorenzo Gerratana, an associate professor at the University of Udine and the principal investigator for the biomarker analysis, emphasized that this analysis demonstrates the utility of CTC counts in identifying metastatic breast cancer patients most likely to benefit from intensified therapy. The findings suggest that those with aggressive disease had significantly better clinical outcomes using combined therapeutic approaches, whereas patients with indolent conditions saw negligible benefits from intensified treatments.

Importantly, understanding the biological mechanisms contributing to resistance against CDK4/6 inhibitors remains an open challenge in the field, creating an urgent demand for reliable biomarkers that can adeptly guide therapeutic decision-making following disease progression.

These conclusions align with the STIC2 trial results published in 2024, which highlighted how treatment decisions based on CTC counts could differ from physician choices, leading to improved survival outcomes or reduction of treatment intensity without compromising survival.

The Future of CTC Testing

Fabio Piazzalunga, President of Menarini Silicon Biosystems, noted that findings from both the STIC and PACE trials illustrate the potential of CELLSEARCH CTC counts to refine treatment of patients within the complexities of metastatic breast cancer, where mechanisms of resistance and disease progression continue to challenge practitioners. The CELLSEARCH CTC test, available for in vitro diagnostic use in Europe and China, is also offered in the United States via the accredited laboratory in Huntingdon Valley, Pennsylvania. The company's mission is to empower healthcare providers to make informed decisions, whether to enhance treatment regimens to manage disease progression or to lessen the intensity of treatments to maintain patients' quality of life.

About CELLSEARCH

CELLSEARCH is the only clinically validated blood test approved by the U.S. FDA for detecting and counting CTCs, aiding physicians in the management of metastatic breast, prostate, and colorectal cancer patients. However, it's essential to note that CELLSEARCH's CTC kit is not authorized for specific therapeutic decision-making guidance, thus underscoring its intended research application beyond sanctioned indications. For more comprehensive information on the intended use and limitations of CELLSEARCH, refer to the user instructions provided on their official documentation website.

Company Background

Menarini Silicon Biosystems, headquartered in Bologna, Italy, and Huntingdon Valley, Pennsylvania, is a wholly owned subsidiary of the Menarini Group, a pharmaceutical, biotechnology, and diagnostic multinational company based in Florence, Italy, employing over 17,000 individuals across 140 countries.