Abstract 478P
Background
Plasma circulating tumor DNA (ctDNA) analysis have therapeutic value in prognosis and monitoring treatment in metastatic colorectal cancer (CRC). Some patients with RAS mutation undergo the clearance of RAS during the treatment, and the incidence rate is 1.6%–20%, as shown in previous studies. This study aimed to present the clearance of RAS mutation in Chinese patients with mCRC harboring RAS mutation.
Methods
Patients with mCRC confirmed by histological results and with RAS mutation confirmed at baseline between May 2018 and December 2019 in Sun Yat-sen University Cancer Center were included (NCT228614). Longitudinal RAS mutation were detected in ctDNA using same Next Generation Sequencing panel every 8 weeks when evaluating tumor response until disease progression (PD). RAS clearance in plasma was defined as the disappearance of RAS mutation concomitantly with at least one gene mutation detectable. Patients who had no serial gene mutations detectable were defined as nonsecretory patients and were excluded from analysis.
Results
A total of 119 patients were enrolled in the study. Among them, 19 nonsecretory patients were excluded. Thirty (30.0%) patients confirmed with RAS clearance (15 cases with clonal mutation including TP53/APC as control gene; 15 cases with new mutations as control gene). Nineteen patients with RAS clearance showed PD, the median progression free survival of patients with RAS clearance and no clearance were 9.5 (95% CI: 7.0, 12.0) months and 10.1 (95% CI: 7.8, 12.4) months (hazard ratio: 0.995; [95% CI: 0.575-1.723]; P=0.986). Table: 478P
RAS mutation clearance in patients with metastatic colorectal cancer
| Patients (n=119) | |
| Nonsecretory patients | 19 (16.0%) |
| Clearance of RAS (n=100) | 30 (30.0%) |
| Gene mutation control (n=30) | |
| Clonal mutation | 15 (50.0%) |
| New mutation | 15 (50.0%) |
| RAS Clearance rate of different RAS variants | |
| KRAS G12X (n=77) | 20 (26.0%) |
| KRAS G13X (n=18) | 4 (22.2%) |
| KRAS Q61X (n=9) | 3 (33.3%) |
| NRAS Q61X (n=6) | 3 (50.0%) |
Conclusions
RAS clearance rate in our study is 30.0%, which was higher than that in the previous study. Monitoring RAS mutation status may be useful for the evaluation of treatment and provide insights for following treatment selection. The association between RAS clearance and prognosis in mCRC needs further investigation.
Clinical trial identification
NCT228614.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.