TEST:

OncoBEAM RAS CRC kit

LB allows the detection of RAS and BRAF mutations in patients deemed RASwt on the basis of tissue analyses. These patients show outcome characteristics expected for RAS- and BRAF-mutant patients in tissue. The study thus confirms the high clinical relevance of LB performed at baseline before the start of therapy.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. Those patients also achieved a significantly greater disease control rate (89% vs 20%; P = 0.008). In conclusion, LB evaluating ctDNA is informative and may help to guide treatment in patients with BRAF V600E-mutated mCRC.

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.

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.

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.

"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.