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Updated: Jul 9, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
RNA Expression-Based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal
Ruoyu Miao1, Dae Won Kim1, James Yu1
1Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Introduction:
We previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response.
Methods:
Twenty-two archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna tumor microenvironment (TME) subtypes were evaluated for correlation with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in TME.
Results:
Based on Xerna™ TME Panel, 4 patients with immune-active (IA) subtype and 6 patients with immune-suppressed subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, p = 0.254), median OS (15.75 vs. 11.9 months, p = 0.378), and higher DCR (70% vs. 58%, p = 0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells.
Conclusion:
Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC.
Insights
The Xerna™ TME Panel may help predict treatment response in refractory metastatic colorectal cancer (CRC) patients receiving regorafenib and nivolumab. Biomarker-positive patients showed trends towards improved survival and disease control, warranting further investigation.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Phase I/Ib study (NCT03712943) investigated regorafenib and nivolumab in refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC).
- The Xerna™ TME Panel, a machine learning-based RNA-sequencing assay, was assessed for its predictive role in treatment response.
Purpose of the Study:
- To investigate the predictive value of the Xerna™ Tumor Microenvironment (TME) Panel in patients with refractory metastatic pMMR CRC treated with regorafenib plus nivolumab.
- To evaluate the correlation between Xerna™ TME subtypes and clinical outcomes (OS, PFS, DCR) and other biomarkers.
Main Methods:
- Twenty-two archival pretreatment tumor samples were analyzed using the Xerna™ TME Panel.
- Xerna™ TME subtypes were correlated with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), KRAS, PD-L1, CD8, and Treg cells.
Main Results:
- Xerna™ TME Panel classified patients into biomarker-positive (immune-active, immune-suppressed) and biomarker-negative (angiogenic, immune desert) subtypes.
- Biomarker-positive patients showed trends towards longer median PFS (7.9 vs. 4.1 months) and OS (15.75 vs. 11.9 months), and higher DCR (70% vs. 58%), though not statistically significant.
- Immune-active subtype correlated with higher Treg cells, while the angiogenic subtype showed lower Treg levels.
Conclusions:
- Xerna™ TME Panel analysis shows potential value in predicting clinical benefit for refractory metastatic pMMR CRC patients treated with regorafenib and nivolumab.
- Further studies are required to confirm the predictive role of the Xerna™ TME Panel in this patient population.
