TEST:

OncoBEAM RAS CRC kit

The incidence of ctDNA RAS MT mCRC was 40.5%, which was associated with liver metastases and high tumor volumes. Anti-EGFR mAb rechallenge may be effective for patients with mCRC who responded to first-line chemotherapy containing anti-EGFR mAb. No patients with RAS MT in ctDNA responded to anti-EGFR mAb rechallenge.

No abstracts available

Conclusions Our prospective observational study revealed the efficacy of anti-EGFR therapy for RAS mutant mCRC pts with RAS mts negative in ctDNA after 1st- or 2nd-line treatment. Further prospective studies need to be conducted for these pts.

Original RAS variants in tissue, tumor diameter, and liver metastasis are related to conversion to NeoRAS WT mCRC in ctDNA.

Our prospective observational study revealed not the least proportion of patients with no RAS mutations in ctDNA after 1st- or 2nd-line treatment in RAS mutant mCRC. Further analysis will be performed to evaluate the efficacy of anti-EGFR antibody treatment for patients with no RAS mutation in ctDNA after standard chemotherapy.

This multi-center study investigated the efficacy of anti-EGFR mAb re-challenge and clinicopathological factors associated with treatment efficacy of anti-EGFR mAb re-challenge that is still unclear in the clinical practice. 74 mCRC patients with tissue RAS/BRAF WT, who were refractory or intolerant to previous chemotherapies, including fluoropyrimidines, oxaliplatin, irinotecan and anti-EGFR mAbs and whose RAS status in ctDNA was examined after prior chemotherapies using ONCOBEAMTM RAC CRC, were enrolled in 4 institutions from June 2021 to December 2022. Re-challenge of anti-EGFR mAb may be effective for patients without RAS mutations detected in ctDNA and those showing response in previous anti-EGFR mAb.

This biomarker study demonstrated the associations between clinical outcomes and IL-8/RAS status in blood before treatment in RAS wild-type mCRC treated with 2nd-line FOLFIRI plus RAM after anti-EGFR antibody therapy. Clinical trial information: UMIN000034885.

107 mCRC patients with tissue RAS MT, confirmed using MEBGEN RASKET-B, who were refractory or intolerant to previous chemotherapies, including fluoropyrimidines, oxaliplatin, or irinotecan were enrolled in 4 institutions from June 2021 to August 2022. Original RAS status in tissue, tumor diameter and liver metastasis are related to conversion to NeoRAS WT mCRC.

"QIAGEN...and Sysmex Inostics combined forces in July 2021 to accelerate global companion diagnostic access. QIAGEN provides unparalleled global custom cancer companion diagnostics (CDx) development and commercialization capabilities utilizing Sysmex Inostics ultra-sensitive NGS liquid biopsy technology...will present the poster "Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials." Circulating tumor DNA (ctDNA) was analyzed and monitored using the Sysmex Inostics OncoBEAM™ RAS CRC Kit."

Among participants of the REMARRY, patients who satisfied the following eligibility criteria were enrolled in PURSUIT; pRAS wild-type within 28 days prior to enrollment in PURSUIT; being refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; and ≥ 4 months of EGFR mAb-free interval. Study treatment was rechallenge with panitumumab 6 mg/kg + irinotecan 150 mg/m2q2wks...Plasma RAS, BRAF V600E, and EGFR extracellular domain mutations were defined as acquired resistances for EGFR mAb. Conclusions Plasma RAS/BRAF/EGFR mutational status after progression on prior EGFR mAb may identify patients with RAS/BRAF V600E wild-type mCRC who could benefit from rechallenge with EGFR mAb.

Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Analysis of ctDNA is a viable strategy for clinical management of mCRC patients. Although the OncoBEAM assay sensitivity is somewhat higher, the fully automated Idylla platform also has good performance, while being cheaper and much less labor-intensive, for the detection of RAS mutations in plasma, either at diagnosis or after progression when considering anti-EGFR treatment rechallenge.

We expect that one patient with no RAS mutations in ctDNA is detected in 100 pts; thus, the sample size of 300 pts is set for our study. Accrual is starting in April 2021.

Our trial aims to confirm the clinical benefit of anti-EGFR mAb rechallenge therapy in patients with plasma RAS negative. Moreover, through biomarker analyses, our trial will shed light on which patients would benefit from rechallenge in addition to being plasma RAS negative.

ctDNA testing by BEAMing seems to be an accurate alternative to tissue testing, especially in the presence of liver metastasis. Repeat RAS testing can be informative at first progression, while the role of RAS MAF as a predictive biomarker needs further study.

SafeSEQ demonstrates clinical sensitivity comparable to OncoBEAM, with a strong positive correlation between MAF values across a broad dynamic range. SafeSEQ also provides expanded coverage across broader genomic regions, which - when combined with robust clinical performance - should better inform treatment selection, improve high resolution monitoring of therapeutic efficacy, and enable MRD detection and surveillance for NSCLC patients.

"The OncoBEAM EGFR V2 is a sensitive, robust, and accurate assay that delivers reproducible results. Next-generation sequencing and BEAMing technologies act complementarily in the routine molecular screening. We show that using a next-generation sequencing assay, despite its lower sensitivity, enables the identification of rare EGFR alterations or resistance mechanisms (mutation, deletion, insertion, and copy number variation) to orient first- and second-line treatments."

The median mutant allele frequency (MAF) for all mutations detected by OncoBEAM was 0.50% (range: 0.04–50.84%), where 64% and 23% of mutations were detected with MAF <1% and <0.1%, respectively. Concordance of results between OncoBEAM and SafeSEQ in 176 replicate samples revealed an overall percent agreement of 99.6% with strong linear correlation of MAF (R2 = 0.98).Conclusions OncoBEAM LB enables sensitive and accurate genotyping results within 5 days, ∼3x faster than the TAT of tissue genotyping results, which carries significant implications for enabling rapid implementation of targeted therapies for NSCLC patients

"Plasma ctDNA-based liquid biopsy in patients with mCRC may be useful depending on the metastatic site. The maximum diameter and lesion number should be carefully considered when determining patients' RAS status with only peritoneal or lung metastases."

In conclusion, both tissue and plasma analyses should be performed for the management of patients with mCRC. To better exploit the beads, emulsions, amplification, magnetics (BEAMing) technique in the clinical setting, studies aimed at determining the RAS status to monitor therapy and during follow-up are warranted.

Legal entity responsible for the study: The authors. Funding: IDICHUS.