TEST:

Oncomine™ Colon cfDNA Assay

Background: In the management of mCRC after progression on irinotecan and oxaliplatin, therapeutic options offer marginal benefit, typically yielding response rates from 1-6%. The CITRIC study is the first randomized trial assessing the efficacy of liquid biopsy for driving anti-EGFR rechallenge in the third line setting. Our preliminary results demonstrate the effectiveness of Cet rechallenge in terms of ORR and DCR and might be considered a treatment option for RAS/BRAF/EGFR-ECD wt ctDNA pts. We will present updated efficacy data at congress.

This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of detectable circulating tumor load after surgery on RFS. Postoperative ctDNA and CTC detection are a strong predictor for a shorter RFS after local treatment, as opposed to preoperative ctDNA or CTC detection.

In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones. In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC.

ctDNA analysis is useful for molecular characterization and tumor response monitoring in patients with mCRC. Quantitative variations of released ctDNA are associated with clinical outcomes.

There is a significant additional yield of NGS in the setting of biliary strictures. Nevertheless, NGS has a limited impact on clinical decision making and for now should only be used in patients in which the outcome is most valuable. This could be to differentiate between different causes of cancer to determine the optimal chemotherapy regimen, or in patients with a clinical suspicion of malignancy but without any mass on cross-sectional imaging.

ctDNA is a potential biomarker to detect MRD after curative treatment for CRLM. Our results demonstrate that out of all patients with detectable ctDNA at baseline (before surgery), ctDNA is still present in 36% of patients three weeks after resection.

The detection of variants in liquid biopsy demonstrates the potential for non-invasive early screening and diagnostic of CRC.

We are now conducting a phase II randomized study, PARERE, to compare panitumumab followed by regorafenib versus the reverse sequence as treatment strategy in anti-EGFR pre-treated chemorefractory pts with RAS/BRAF wt ctDNA. This is the largest series of pts prospectively screened for anti-EGFR re-tx. Around one out of 3 pts bear RAS or BRAF mutations in their ctDNA. Anti-EGFR free interval is not a valuable surrogate of ctDNA mutational status, thus supporting liquid biopsy as a selection tool for clinical trials in this setting and for the use of anti-EGFR re-tx in the real life.

We are now conducting a phase II randomized study, PARERE, to compare panitumumab followed by regorafenib versus the reverse sequence as treatment strategy in anti-EGFR pre-treated chemorefractory pts with RAS/BRAF wt ctDNA. About 1 out of 3 pts bear RAS or BRAF mut in their ctDNA. Anti-EGFR free interval is not a valuable surrogate of ctDNA mut status, thus supporting liquid biopsy as a selection tool for clinical trials in this setting and for the use of anti-EGFR re-tx in the real life.

In this retrospective exploratory study, we evaluated the utility of ctDNA analysis in a series of 53 mCRC patients treated with chemotherapy plus bevacizumab in first-line...Conclusions The mutational analysis performed on ctDNA is useful for mCRC molecular characterization, and quantitative variations of released ctDNA are associated with clinical outcomes. Together these results support the use of liquid biopsy for both molecular characterization and tumor response monitoring in mCRC patients.

"A research grant and drug supply during panitumumab-based maintenance treatment was provided by Amgen...We identified 15.32% as the optimal VAF cut off for survival prediction. Conclusions ctDNA VAF should be prospectively investigated as a prognostic marker and may be useful for estimating disease burden compared to physician experience, CEA and CT scans."