KEY TAKEAWAYS
- The PERMAD phase 2 trial aimed to investigate CAF as biomarkers for predicting resistance to FOLFOX + bevacizumab in pts with mCRC.
- Researchers noticed that the CAF marker combo predicts FOLFOX+bevacizumab resistance in pts with mCRC.
Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are integral in metastatic colorectal cancer (mCRC) treatment, lacking reliable resistance biomarkers. A biomarker-guided strategy could enhance outcomes by predicting resistance early through cytokine and angiogenic growth factor (CAF) analysis using machine learning, potentially 100 days pre-radiologic staging for FOLFOX plus bevacizumab.
Thomas Seufferlein and the team aimed to assess the efficacy of this biomarker-guided approach in predicting resistance to first-line treatment with FOLFOX plus bevacizumab in patients (pts) with mCRC.
They performed an inclusive analysis across 15 centers, enrolling 50 pts with mCRC undergoing first-line FOLFOX plus bevacizumab treatment. Plasma samples were collected biweekly until radiologic progression (RECIST 1.1) assessed by CT scans every 2 months. A panel of 102 pre-selected CAFs was centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM).
By using random forests, a predictive machine learning model was developed to distinguish between “no progress within 100 days before radiological progress” and “progress within 100 days before radiological progress”. A combination of 10 out of the 102 CAF markers achieved 78.2% accuracy, 71.8% sensitivity, and 82.5% specificity in this task.
The study concluded that a specific combination of CAF markers identifies treatment resistance to FOLFOX plus bevacizumab in pts with mCRC within 100 days before radiologic progression.
The trial was sponsored by the University of Ulm.
Source: https://pubmed.ncbi.nlm.nih.gov/38875244/
Clinical Trial: https://clinicaltrials.gov/study/NCT02331927
Seufferlein T, Lausser L, Stein A, et al. (2024). “Prediction of resistance to bevacizumab plus FOLFOX in metastatic colorectal cancer-Results of the prospective multicenter PERMAD trial.” PLoS One. 2024 Jun 14;19(6):e0304324. doi: 10.1371/journal.pone.0304324. PMID: 38875244; PMCID: PMC11178165.
