591P - Survival and benefit of adjuvant chemotherapy (ACT) by circulating tumor DNA (ctDNA)-based genomic profile and molecular residual disease (MRD) in resectable colorectal oligometastases (CRM): PRECISION, a prospective multicenter study

Background

The utility of ctDNA analysis in guiding personalized ACT for resectable CRM remains unclear.

Methods

Patients (pts) with previously untreated resectable CRM scheduled for curative resection were prospectively enrolled between March 2021 and October 2022. Pretreatment genomic alterations were detected using Guardant360, a 74-gene ctDNA profiling assay, while postoperative 4-week MRD was assessed using Guardant Reveal, a methylation-based ctDNA MRD assay.

Results

Of 118 eligible pts enrolled, pretreatment ctDNA was detected in 99 pts (84%), 62 (53%) of whom had poor genomic profile, predetermined to have at least one of BRAF, RAS, PIK3CA, or SMAD4 mutations. Of 110 pts who underwent surgery for CRM, postoperative 4-week MRD was detected in 26 (22%) pts. Eighteen patients (16%) had both pretreatment poor genomic profile and positive MRD. With a median follow-up time of 11.0 months (m), median recurrence-free survival (RFS) was 15.2 m. Poor genomic profile (hazard ratio [HR], 2.26 [95% CI, 1.00–5.10]) and MRD positivity (HR, 3.85 [95% CI, 1.79–8.30]) were significantly associated with shorter RFS in multivariate analysis. Positive MRD was associated with shorter RFS (HR, 5.04 [95% CI, 2.30–11.05]) in the poor genomic profile group but not in those without poor genomic profile. Patients with poor genomic profile and positive MRD derived significant benefit from ACT (median RFS, 8.0 m vs. 2.0 m; HR, 0.25 [95% CI, 0.07–0.82]), while no significant benefit was observed in other groups.

Conclusions

Pretreatment genomic profile and postoperative MRD by ctDNA analysis accurately stratify the prognosis and may guide personalized ACT in pts with resectable CRM.

Clinical trial identification

UMIN000042490.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Japan Agency for Medical Research and development.

Disclosure

E. Oki: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bayer, Eli Lilly, Bristol Myers Squibb, MSD; Financial Interests, Personal and Institutional, Research Grant: Guardant Health. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health AMEA; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics; Financial Interests, Institutional, Invited Speaker: Seagen. All other authors have declared no conflicts of interest.