{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:45:07Z","timestamp":1792104307653,"version":"4.4.0"},"reference-count":3,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      CUPISCO (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03498521\">NCT03498521<\/jats:ext-link>\n                      ) 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). We report efficacy and safety after &gt;1 year of additional follow-up. Eligible patients were randomly assigned (3:1) to MGT (investigator-chosen after discussion in a molecular tumor board) or three further cycles of chemotherapy. The primary end point was PFS. Secondary end points included overall survival (OS) and safety. At data cutoff (December 6, 2024), 436 patients were randomly assigned (326 to MGT; 110 to chemotherapy). Median follow-up was 37.0 months (range, 0.0-67.8). Updated median PFS was 6.1 months (95% CI, 4.7 to 6.5) with MGT and 4.4 months (95% CI, 4.2 to 6.4) with chemotherapy (hazard ratio [HR], 0.75 [95% CI, 0.59 to 0.95];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .017); median OS was 15.2 months (95% CI, 13.9 to 18.4) and 12.8 months (95% CI, 9.8 to 15.4), respectively (HR, 0.79 [95% CI, 0.61 to 1.02];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0689). No new safety signals were identified. These updated results aligned with the primary analysis, demonstrating the benefit of CGP with subsequent MGT and highlighting the importance of incorporating CGP at initial diagnosis to guide treatment decisions for patients with unfavorable CUP.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02974","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:59:11Z","timestamp":1788465551000},"page":"2895-2902","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Molecularly Guided Therapy Versus Continued Chemotherapy in Unfavorable Cancer of Unknown Primary: Updated Efficacy and Safety From the Randomized, Phase II CUPISCO Study"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct03498521","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8232-9982","authenticated-orcid":false,"given":"Alwin","family":"Kr\u00e4mer","sequence":"first","affiliation":[{"name":"Clinical Cooperation Unit Molecular Hematology\/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany"},{"name":"Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4162-7881","authenticated-orcid":false,"given":"Tilmann","family":"Bochtler","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Molecular Hematology\/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany"},{"name":"Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany"},{"name":"Department of Medical Oncology, Heidelberg University Hospital, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Pauli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Z\u00fcrich, Z\u00fcrich, Switzerland"},{"name":"Medical Faculty, University of Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6202-9640","authenticated-orcid":false,"given":"Kai-Keen","family":"Shiu","sequence":"additional","affiliation":[{"name":"UCLH Gastrointestinal Oncology Service, Cancer of Unknown Primary Service, UCL Cancer Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-1082","authenticated-orcid":false,"given":"Natalie","family":"Cook","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Manchester, United Kingdom"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-2324","authenticated-orcid":false,"given":"Juliana","family":"Janoski de Menezes","sequence":"additional","affiliation":[{"name":"Clinical Oncology, Centro Pesquisa Integrado em Oncologia, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Pazo-Cid","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Miguel Servet University Hospital, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Losa","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Sant Joan Desp\u00ed Mois\u00e8s Broggi, ICO L'Hospitalet, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-9991","authenticated-orcid":false,"given":"Debbie G.J.","family":"Robbrecht","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-9103","authenticated-orcid":false,"given":"Ji\u0159\u00ed","family":"Tom\u00e1\u0161ek","sequence":"additional","affiliation":[{"name":"Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-7432","authenticated-orcid":false,"given":"Cagatay","family":"Arslan","sequence":"additional","affiliation":[{"name":"\u0130zmir University of Economics, Medical Point Hospital, \u0130zmir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8417-8628","authenticated-orcid":false,"given":"Mustafa","family":"\u00d6zg\u00fcro\u011flu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, Cerrahpasa Faculty of Medicine, Istanbul University Cerrahpasa, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panoraia","family":"Arni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany"},{"name":"Department of Medical Oncology, European Interbalkan Medical Center, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Bigot","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut de Canc\u00e9rologie de l'Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5886-3920","authenticated-orcid":false,"given":"Sun Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-9064","authenticated-orcid":false,"given":"Yoichi","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-5351","authenticated-orcid":false,"given":"Antoine","family":"Italiano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institut Bergoni\u00e9, Bordeaux, France"},{"name":"University of Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nass\u00e9ra","family":"Chalabi","sequence":"additional","affiliation":[{"name":"Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Dur\u00e1n-Pacheco","sequence":"additional","affiliation":[{"name":"Global Product Development Data and Statistical Sciences, F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"Late-Stage and Marketed Medicines Safety, Product Development Safety, Genentech, Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Scarato","sequence":"additional","affiliation":[{"name":"Clinical Development and Medical Affairs, Roche Diagnostics, F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-2596","authenticated-orcid":false,"given":"Jeffrey S.","family":"Ross","sequence":"additional","affiliation":[{"name":"Pathology Group, Foundation Medicine, Inc, Cambridge, MA;"},{"name":"Department of Pathology, Upstate Medical University, Syracuse, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Moch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Z\u00fcrich, Z\u00fcrich, Switzerland"},{"name":"Medical Faculty, University of Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-6014","authenticated-orcid":false,"given":"Linda","family":"Mileshkin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_11_2_2","first-page":"1092","article-title":"Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): An open-label, randomised, phase 2 study","volume":"25","author":"Kr\u00e4mer A","year":"2024","unstructured":"Kr\u00e4mer A, Bochtler T, Pauli C, et al: Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): An open-label, randomised, phase 2 study. Lancet 25:1092-1102, 2024","journal-title":"Lancet"},{"key":"e_1_3_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.2205"},{"key":"e_1_3_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"}],"updated-by":[{"DOI":"10.1200\/jco-26-02285","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000}}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-02974","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:59:35Z","timestamp":1792101575000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-02974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":3,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,10,20]]}},"alternative-id":["10.1200\/JCO-25-02974"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-02974","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-27","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}