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Pretreatment Plasma Circulating Tumor DNA RAS/BRAF Mutational Status in Refractory Metastatic Colorectal Cancer
Davide Ciardiello1,2, Stefania Napolitano1, Vincenzo Famiglietti1
1Medical Oncology Unit, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.
Abstract:
Rechallenge with anti-EGFR drugs represents a promising strategy in refractory RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC). We performed the pooled analysis of the CAVE and VELO studies to evaluate the percentage of patients with WT circulating tumor DNA (ctDNA) tumors and the association of mutational status with time from the last anti-EGFR drug administration. At baseline, 97/129 patients had RAS/BRAF WT plasma ctDNA, while 32/129 had RAS/BRAF mutated plasma ctDNA. Median anti-EGFR drug-free interval was 10.6 (CI 95%, 8.9-13.4) months in the plasma RAS/BRAF mutant group as compared to 13.0 (CI 95%, 11.1-16.6) months in RAS/BRAF WT group (p = 0.169). To investigate the time window of the RAS/BRAF mutant cancer cell clone disappearance, descriptive analysis using different time points was performed. No difference in the proportion of patients whose baseline plasma ctDNA was RAS/BRAF WT or mutated was found between 4 and 18 months since the last administration of anti-EGFR drugs. In contrast, 38/44 of patients with anti-EGFR drug-free interval of 18 months or more displayed a ctDNA RAS/BRAF WT status. Taken together, these results shows that the length of anti-EGFR free interval is not a sufficient criterion for patient selection, supporting the role of liquid biopsies for improving treatment efficacy.
Insights
Rechallenging patients with metastatic colorectal cancer (mCRC) using anti-EGFR drugs requires careful selection. Liquid biopsies detecting circulating tumor DNA (ctDNA) can identify patients with RAS/BRAF wild-type (WT) status, improving treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Rechallenge with anti-EGFR drugs is a potential strategy for refractory RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC).
- Patient selection for anti-EGFR rechallenge is critical, and the role of circulating tumor DNA (ctDNA) needs further investigation.
Purpose of the Study:
- To evaluate the percentage of patients with WT ctDNA at baseline in mCRC.
- To assess the association between RAS/BRAF mutational status in plasma ctDNA and the duration of the anti-EGFR drug-free interval.
Main Methods:
- Pooled analysis of the CAVE and VELO studies.
- Detection of RAS/BRAF mutations in plasma ctDNA at baseline.
- Descriptive analysis of ctDNA mutational status at different time points after the last anti-EGFR drug administration.
Main Results:
- At baseline, 97/129 patients had RAS/BRAF WT plasma ctDNA, while 32/129 had mutated plasma ctDNA.
- No significant difference in the anti-EGFR drug-free interval was observed between RAS/BRAF WT and mutant groups (13.0 vs 10.6 months).
- A significant proportion of patients (38/44) with an anti-EGFR drug-free interval of 18 months or more showed WT ctDNA status.
Conclusions:
- The duration of the anti-EGFR drug-free interval alone is insufficient for selecting patients for rechallenge therapy.
- Liquid biopsies analyzing ctDNA are crucial for improving patient selection and treatment efficacy in RAS/BRAF WT mCRC rechallenge settings.
