592P - The role of early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer

Background

There remains a need to improve the method to predict the therapeutic effect of metastatic colorectal cancer (mCRC). The aim of this study is to explore the value of early change in circulating tumor DNA (ctDNA) as a biomarker for prediction of the drug efficacy of chemotherapy in mCRC (NCT04555369).

Methods

Patients with mCRC treated with first-line chemotherapy (including clnical routine regimens such as XELOX, FOLFIRI, mFOLFOX6 with or without cetuximab or bevacizumab) were enrolled in this study. Plasma ctDNA was detected at baseline and before the second cycle of chemotherapy, and the mutation of 25 tumor-related genes in ctDNA were detected by next generation screen technology. The primary endpoint of this study is to evaluate the role of early change of ctDNA in predicting ORR (objective response rate).

Results

From Sep. 2020 to Sep.2022, 209 mCRC patients treated with first-line chemotherapy were enrolled in this study.The median follow-up time was 331 days. Among these 209 patients, the ctDNA mutations were detected in 84.21% of patients at baseline. The most frequently mutated genes were TP53 (60.29%), APC (56.94%) and KRAS (34.93%) gene. The value of MSAF (maximum somatic allele frequency) change after the first cycle of chemotherapy was significantly different between tumor remission and non-remission groups (P=0.001). The cut-off value of MSAF change for predicting tumor remission was 6.27% (AUC 0.637,95%CI:0.556-0.719, P=0.002). The ORR were 54.2% and 31.4% in patients with MSAF change ≥ 6.27% group and ＜ 6.27% group (P=0.003), while DCR (disease control rate) were 95.3% and 91.4% (P = 0.347) in these two groups, respectively. In addition, the K-M survival curve and log-rank test showed that PFS (progression free survival) were significantly different in the two groups (median PFS of MSAF change ≥ 6.27% group vs. MSAF change ＜ 6.27% group: 317 days vs. 217 days; HR:1.598, 95%CI:1.016-2.514, P=0.03).

Conclusions

The early changes in ctDNA levels after initiation of first-line chemotherapy in mCRC would enable early prediction of response prior to radiological assessment.

Clinical trial identification

NCT04555369.

Editorial acknowledgement

Legal entity responsible for the study

Ethical Committees of Fudan University Shanghai Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.