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

Background

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.

Methods

RAS mutant mCRC pts with refractory or intolerable after response to prior fluoropyrimidine-containing regimen were enrolled. OncoBEAM^TM 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.

Results

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).

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.

Clinical trial identification

UMIN000043442.

Editorial acknowledgement

Legal entity responsible for the study

Japan Clinical Cancer Research Organization.

Funding

Sysmex.

Disclosure

All authors have declared no conflicts of interest.