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Background <p>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.</p> Methods <p>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.</p> Results <p>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)&#xa0;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 &lt;1%).</p> Discussion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • 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

摘要

Background

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.

Methods

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.

Results

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%).

Discussion

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.