CUPCOMP: A multi-site UK trial in carcinoma of unknown primary: A comparison across tissue and liquid biomarkers.

• DOI: 10.1200/jco.2024.42.16_suppl.3059
• Publication Date: 2024-06-14T17:01:38Z
• Authors: Alicia-Marie Conway; Matthew Robinson; Matthew Concannon; Sally Clive; Tania Tillett; Kai-Keen Shiu; Louise C. Medley; Sonali Dasgupta; Eliyaz Ahmed; Kelly Warrington; Zoulikha Zair; Tess Gillham; Aaron Davis; Julie-Anne Scott; Alison Taylor; Mark Stares; Claire Mitchell; Pedro Oliveria; George Burghel; Natalie Cook
• Keywords: 03 medical and health sciences; 0302 clinical medicine

3059 Background: Cancer of Unknown Primary (CUP) is a difficult to treat cancer entity for which the tumour origins remain elusive. There emerging evidence support precision medicine approach aid treatment decisions, however scarcity tissue molecular profiling remains challenge. CUPCOMP sought compare feasibility from both and blood in patients (pts) diagnosed with CUP. Methods: A non-randomised prospective clinical trial conducted across 7 UK sites between 06/2021-02/2023. Eligible pts had histological confirmed diagnosis favourable/unfavourable CUP based on clinical, radiological, pathological review at Multi-Disciplinary Team meeting ESMO Guidelines Pts mutation performed circulating DNA (ctDNA) (FoundationOne Liquid CDx) CDX or whole genome sequencing (WGS)). All results were discussed dedicated Molecular Tumour Board (MTB) evaluate activation state oncogenic pathways. Results: Baseline characteristics 117 recruited are shown (Table). 114/117 (97%) successful (109/117; 93% pts) (69/117; 59% profiling; methods 64/117 (55%) pts. WGS was only 15/21 where repeat biopsy obtained. Where targeted using same panel (49/117; 42%): 421/550 (77%) Single Nucleotide Variants (SNVs) found concordant ctDNA. ctDNA fraction ≥10% 41/109 (35%) In ctDNA, 1556 SNVs, 271 genes, 42 rearrangements identified. 73/114 (64%) cases carried an actionable alteration tissue, as determined by MTB. The most frequently reported gene alterations were: KRAS (n=11; 10%); ATM (n=9; 8%); ARID1A PIK3CA (n=10; 9%); NF2 (n=7; 6%); BRAF FGFR2-fusion 6%). mutational burden (TMB) ≥10 mutations/Mb detected 25/117 (22%) Potential germline variants 8% 80/114 (70%) alive 6 months after consent trial. Conclusions: Successful tissue-based challenging CUP; achieved this cohort. analysis feasible (93% successful) reliably tissue. Potentially 64% should be considered reliable alternative testing Clinical information: NCT04750109 . [Table: see text]