Efficacy of an anti-EGFR after ctDNA conversion from mutated RAS status of metastatic colorectal cancer: Results of a pilot study.

Abstract

e15574 Background: This pilot study aimed at the evaluation of the efficacy of anti-EGFR therapy in patients with initially RAS-mutated metastatic colorectal cancer, whose liquid biopsy found no RAS mutation after prior chemotherapy failure. Methods: Sixteen patients with RAS-mutated metastatic colorectal cancer in the solid tumor were included, after they had received 1 to 3 prior chemotherapy lines without anti-EGFR. Before inclusion, RAS genotyping was performed in circulating tumor DNA (ctDNA) from liquid biopsy, after a median duration of ̃24 months after the initial RAS status determination. No RAS mutation was detected in the circulating tumor DNA from 9 patients (56%), who then received cetuximab-FOLFIRI. The 7 patients who had persistent RAS mutation in the liquid biopsy (44%) were treated according to standard recommendations without anti-EGFR. Results: The median progression free survival was 8.2 months [95%CL, 4.5 – 11.8] in patients without detectable ctDNA RAS mutation, as compared to 3.5 months [2.1 – 4.9] in the ctDNA mutated patients (p < 0.001). The median overall survival was 22.3 months [17.3 - 27.3] in the patients with undetectable ctDNA RAS mutation, whereas it was 4.7 months [2.6 - 6.7] in those with ctDNA RAS mutation (p = 0.013). These results suggested the efficacy of cetuximab-based chemotherapy in patients with initially RAS mutated metastatic colorectal cancer, who later displayed no detectable ctDNA RAS mutation. Conclusions: The introduction of an anti-EGFR could provide an additional treatment option for patients with metastatic colorectal cancer with apparent conversion of initial RAS mutation, based on ctDNA assessment after prior failure on anti-EGFR-free chemotherapy.