594P The efficacy of anti-EGFR therapy for RAS mutant metastatic colorectal cancer (mCRC) patients with RAS mutation negative in circulating-tumor DNA (ctDNA) after 1st- or 2nd-line chemotherapy

Liquid biopsy studies have shown the change of RAS status in ctDNA after chemotherapy in RAS wild-type mCRC. Our prospective observational study (RASMEX study) showed that the rate of RAS mutant mCRC patients (pts) with RAS mutations (mts) negative in ctDNA after standard chemotherapy was 22.8% (Izawa, et al, JSMO annual meeting 2023). Here, we present the efficacy of anti-epidermal growth factor receptor (EGFR) therapy for these pts. RAS mutant mCRC pts with refractory or intolerable after response to prior fluoropyrimidine-containing regimen were enrolled. OncoBEAMTM RAS CRC kit was used to measure RAS mts in ctDNA just after 1st- or 2nd-line treatment. For pts with RAS mts negative in ctDNA who received anti-EGFR therapy after enrollment, the overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were prospectively evaluated. In RAS mts negative pts in ctDNA, blood samples were also collected before anti-EGFR therapy and RAS/BRAF/PIK3CA mts were measured by Plasma-SeqSensei TM CRC RUO Kit. Of 55 (22.8%) had RAS mts negative in ctDNA among 241 pts who filled the eligibility criteria, 29 received chemotherapy including anti-EGFR antibody: median age, 66 years; left-sided primary tumor, 79.3%; 11 pts for 2nd-line setting and 18 pts for 3rd- or later-line setting. In 11 pts receiving 2nd-line combination chemotherapy, ORR and DCR were 0% and 54.5% (95% confidence interval [CI]: 25.1–84.0), respectively. The median PFS was 4.9 months (95%CI: 1.9–6.5). In 8 pts without any mts in ctDNA before treatment, DCR was 62.5% and median PFS was 5.6 months. While, ORR and DCR were 5.6% (95%CI: 0–16.1) and 55.6% (95%CI: 32.6–78.5), respectively, in 18 pts receiving 3rd- or later-line treatment with combo- or monotherapy. The median PFS was 3.3 months (95%CI: 1.6–4.8). In 12 pts without any mts in ctDNA before treatment, ORR and DCR both were better (8.3% and 58.3%, respectively). 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.