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Peer-Reviewed Publication
J Clin Oncol2026;JCO2502974.September 3, 2026Journal Article

Molecularly Guided Therapy Versus Continued Chemotherapy in Unfavorable Cancer of Unknown Primary: Updated Efficacy and Safety From the Randomized, Phase II CUPISCO Study.

Alwin Krämer1,2, Tilmann Bochtler1,2,3, Chantal Pauli4,5, Kai-Keen Shiu6, Natalie Cook7,8, Juliana Janoski de Menezes9, Roberto A Pazo-Cid10, Ferran Losa11, Debbie G J Robbrecht12, Jiří Tomášek13, Cagatay Arslan14, Mustafa Özgüroğlu15, Panoraia Arni16,17, Frederic Bigot18, Sun Young Kim19, Yoichi Naito20, Antoine Italiano21,22, Nasséra Chalabi23, Gonzalo Durán-Pacheco24, Ning Ma25, Jeremy Scarato26, Jeffrey S Ross27,28, Holger Moch4,5, Linda Mileshkin29
1Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
3Department of Medical Oncology, Heidelberg University Hospital, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
4Department of Pathology and Molecular Pathology, University Hospital Zürich, Zürich, Switzerland.
5Medical Faculty, University of Zürich, Zürich, Switzerland.
6UCLH Gastrointestinal Oncology Service, Cancer of Unknown Primary Service, UCL Cancer Institute, London, United Kingdom.
7The Christie NHS Foundation Trust, Manchester, United Kingdom.
8Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
9Clinical Oncology, Centro Pesquisa Integrado em Oncologia, Porto Alegre, Brazil.
10Medical Oncology Department, Miguel Servet University Hospital, Zaragoza, Spain.
11Medical Oncology Department, Hospital de Sant Joan Despí Moisès Broggi, ICO L'Hospitalet, Barcelona, Spain.
12Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
13Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
14İzmir University of Economics, Medical Point Hospital, İzmir, Türkiye.
15Department of Internal Medicine, Division of Medical Oncology, Cerrahpasa Faculty of Medicine, Istanbul University Cerrahpasa, Istanbul, Türkiye.
16Department of Medical Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany.
17Department of Medical Oncology, European Interbalkan Medical Center, Thessaloniki, Greece.
18Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France.
19Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
20Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan.
21Department of Medicine, Institut Bergonié, Bordeaux, France.
22University of Bordeaux, Bordeaux, France.
23Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
24Global Product Development Data and Statistical Sciences, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
25Late-Stage and Marketed Medicines Safety, Product Development Safety, Genentech, Inc., South San Francisco, CA.
26Clinical Development and Medical Affairs, Roche Diagnostics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
27Pathology Group, Foundation Medicine, Inc., Cambridge, MA.
28Department of Pathology, Upstate Medical University, Syracuse, NY.
29Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
PubMed DOI

Abstract

CUPISCO (ClinicalTrials.gov identifier: NCT03498521) demonstrated longer progression-free survival (PFS) with comprehensive genomic profiling (CGP) and subsequent molecularly guided therapies (MGTs), versus standard platinum-based chemotherapy, in patients with previously untreated, unfavorable cancer of unknown primary (CUP) who reached disease control after induction chemotherapy (three cycles).…

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