Abstract 72P
Background
Patients with metastatic colorectal cancer (mCRC) demonstrate inconsistent RAS status before and after treatment. Some tumors develop RAS mutation as a mechanism of resistance to anti-EGFR. Conversely, following chemotherapy, a number of individuals with RAS-mut mCRC lose their mutation and develop a RAS-wt status, making the NeoRAS phenomenon an important aspect of mCRC treatment. The objective of this study is to characterize the RAS mutational status change in patients who have progressed after a first-line therapy regimen through the use of liquid biopsy.
Methods
This study is part of the Lebanese NEORAS trial. It is a phase IV, observational of Lebanese patients diagnosed with mCRC and followed-up during the course of their treatment. At diagnosis, the tumor RAS status was tested with liquid biopsy and confirmed by a tissue biopsy. Patients were followed up monthly after their diagnosis, and upon confirmed clinical progression, and before initiation of a second-line therapy a liquid biopsy to monitor the mutational profile of the tumor using the Idylla RT-PCR platform.
Results
One hundred patients were initially enrolled. Forty-three 43 out of the 100 patients have progressed on their first line of therapy. At baseline testing, before chemotherapy initiation, 25 (58%) patients had a RAS-mut tumor with a mutation being found at least on the tissue or the liquid biopsy and 18 (42%) patients had a RAS-wt phenotype. Upon progression after first-line therapy, 20 of the 25 (80%) patients initially RAS-mut patients conserved their mutation while 5 (20%) shifted towards a RAS-wt phenotype after one line of therapy. Conversely, 16 of the 18 (89%) patients who were initially RAS-wt conserved this phenotype while 2 (11%) patients developed a RAS mutation.
Conclusions
In conclusion, this study has characterized of RAS mutational shift after mCRC first-line treatment using liquid biopsy. The best time for retesting has not yet been established. Further studies are needed to assess the best strategy for RAS status monitoring.
Legal entity responsible for the study
The authors.
Funding
Merck, KGaA, Darmstadt, Germany, Biocartis.
Disclosure
All authors have declared no conflicts of interest.