Correlation Of Braf Mutation Status In Circulating Tumour Dna (Ctdna) With Tumour Biopsy And Clinical Outcomes In Columbus

ctDNA testing offers a less invasive alternative to biopsy for identifying BRAF-positive patients (pts) with melanoma who are candidates for targeted therapy, and may have prognostic value. We assessed the concordance between ctDNA and tumour tissue BRAF mutation status, and clinical relevance of ctDNA BRAF mutation status, using data from COLUMBUS. In COLUMBUS part 1, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID, encorafenib 300 mg QD or vemurafenib 960 mg BID. A total of 613 plasma samples were collected during screening. BRAF V600E/K in ctDNA were assessed using BEAMing technology, and concordance of BRAF status between baseline (BL) ctDNA and tissue was assessed. Associations of ctDNA BRAF V600E/K mutation status (yes/no) with BL markers of poor prognosis and centrally confirmed overall response rates (ORRs) were analysed. Data are as-is and the trial is ongoing. In total, 502 pts had results for both ctDNA and tissue BRAF V600E/K assessments. Of these pts, 317 (63%) had BRAF V600E/K detected by ctDNA, and 420 (84%) had BRAF V600E/K by tissue. Overall agreement (positive agreement; negative agreement) of ctDNA versus tumour tissue was 78% (75%; 96%) for BRAF V600E/K, 81% (75%; 99%) for BRAF V600E and 97% (70%; 99%) for BRAF V600K. BRAF V600E/K detectable by ctDNA were associated with higher lactate dehydrogenase levels, greater number of organs with disease, and greater tumour burden at BL (unadjusted Wilcoxon 2-sample p<0.0001 for each). Within each treatment arm, there were no notable ORR differences between ctDNA BRAF mutation status (95% CIs overlapped; Table). These findings confirm the reliability of ctDNA for detecting BRAF mutations; ctDNA may serve as an alternative test for BRAF V600E/K mutations. ctDNA BRAF mutations correlated with BL markers of poor prognosis but not with ORR.Table: 1127PctDNA BRAF mutation status and ORR by treatment armctDNA BRAF V600E/K mutationCentrally confirmed ORR, % (95% CI)Encorafenib 450 mg QD + binimetinib 45 mg BIDEncorafenib 300 mg QDVemurafenib 960 mg BIDYes69.3 (57.6–79.5)57.5 (45.9–68.5)42.3 (31.2–54.0)No53.3 (34.3–71.7)60.0 (38.7–78.9)40.7 (22.4–61.2) Open table in a new tab