A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP).

Authors

Alicia-Marie Conway, Matthew Robinson, Matthew Concannon, Sally Clive, Tania Tillett, Kai-Keen Shiu, Louise Medley, Sonali Dasgupta, Eliyaz Ahmed, Kelly Warrington, Usman Mahmood, Zoulikha Zair, Tess Gillham, Aaron Davis, Julie-Anne Scott, Alison Taylor, Mark Stares, Claire Mitchell, Pedro Oliviera, George J Burghel, Natalie Cook

Published in

British journal of cancer. Jul 20, 2026. Epub Jul 20, 2026.

Abstract

Cancer of Unknown Primary (CUP) is an aggressive malignancy with poor patient outcomes. For most patients, the primary site remains elusive, limiting therapeutic options to non-specific chemotherapy. The CUP-COMP study (NCT04750109) assessed the feasibility of integrating molecular profiling with a National Molecular Tumour Board (MTB) into the treatment pathway of patients with CUP.
Patients with histologically confirmed CUP were recruited from seven UK sites. Blood- and/or tissue-based molecular profiling was performed with results interpreted via an MTB identifying potentially actionable alterations (PAA). Retrospective tissue and blood alteration analysis assessed concordance and utility.
113/117 patients recruited between June 2021 and February 2023 completed 12 months of follow-up. Of 115 patients with successful molecular profiling, blood-based profiling was more successful (93%) than tissue-based (61%). The MTB identified PAAs in 63% (73/115), with 26% (31/117) treated using a precision medicine (PM) approach. Primary tumours were subsequently confirmed/suspected in 41 patients. Median overall survival (OS) was 9.5 months. Detecting a PAA in blood was impacted by tumour fraction (33% of patients had a tumour fraction <1%).
CUP-COMP demonstrates liquid biopsies are highly feasible in CUP. While tissue profiling remains preferable, blood-based profiling offers a timely viable alternative to tissue, especially in selected patients.

PMID:
42477427
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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