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Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study
A. Krämer, T. Bochtler, C. Pauli, KK. Shiu, N. Cook, JJ. de Menezes, RA. Pazo-Cid, F. Losa, DG. Robbrecht, J. Tomášek, C. Arslan, M. Özgüroğlu, M. Stahl, F. Bigot, SY. Kim, Y. Naito, A. Italiano, N. Chalabi, G. Durán-Pacheco, C. Michaud, J....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, klinické zkoušky, fáze II, randomizované kontrolované studie, multicentrická studie, srovnávací studie
NLK
ProQuest Central
od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest)
od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
- MeSH
- adenokarcinom farmakoterapie MeSH
- cílená molekulární terapie MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory neznámé primární lokalizace * farmakoterapie genetika MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: Patients with unfavourable subset cancer of unknown primary (CUP) have a poor prognosis when treated with standard platinum-based chemotherapy. Whether first-line treatment guided by comprehensive genomic profiling (CGP) can improve outcomes is unknown. The CUPISCO trial was designed to inform a molecularly guided treatment strategy to improve outcomes over standard platinum-based chemotherapy in patients with newly diagnosed, unfavourable, non-squamous CUP. The aim of the trial was to compare the efficacy and safety of molecularly guided therapy (MGT) versus standard platinum-based chemotherapy in these patients. This was to determine whether the inclusion of CGP in the initial diagnostic work-up leads to improved outcomes over the current standard of care. We herein report the primary analysis. METHODS: CUPISCO was a phase 2, prospective, randomised, open-label, active-controlled, multicentre trial done at 159 sites in 34 countries outside the USA. Patients with central eligibility review-confirmed disease (acceptable histologies included adenocarcinoma and poorly differentiated carcinoma) and an Eastern Cooperative Oncology Group performance status of 0 or 1, evaluated by CGP, who reached disease control after three cycles of standard first-line platinum-based chemotherapy were randomly assigned 3:1 via a block-stratified randomisation procedure to MGT versus chemotherapy continuation for at least three further cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03498521, and follow-up is ongoing. FINDINGS: From July 10, 2018, to Dec 9, 2022, 636 (42%) of 1505 screened patients were enrolled. Median follow-up in the treatment period was 24·1 months (IQR 11·6-35·6). Of 438 patients who reached disease control after induction chemotherapy, 436 were randomly assigned: 326 (75%) to the MGT group and 110 (25%) to the chemotherapy group. Median progression-free survival in the intention-to-treat population was 6·1 months (95% CI 4·7-6·5) in the MGT group versus 4·4 months (4·1-5·6) in the chemotherapy group (hazard ratio 0·72 [95% CI 0·56-0·92]; p=0·0079). Related adverse event rates per 100-patient-years at risk were generally similar or lower with MGT versus chemotherapy. INTERPRETATION: In patients with previously untreated, unfavourable, non-squamous CUP who reached disease control after induction chemotherapy, CGP with subsequent MGTs resulted in longer progression-free survival than standard platinum-based chemotherapy. On the basis of these results, we recommend that CGP is performed at initial diagnosis in patients with unfavourable CUP. FUNDING: F Hoffmann-La Roche.
Clinical Oncology Centro Integrado de Pesquisa em Oncologia Porto Alegre Brazil
Department of General Internal Medicine National Cancer Center Hospital East Kashiwa Japan
Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany
Department of Medical Oncology Institut de Cancérologie de l'Ouest Angers France
Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne VIC Australia
Department of Oncology Asan Medical Center University of Ulsan College of Medicine Seoul South Korea
Department of Pathology and Molecular Pathology University Hospital of Zurich Zurich Switzerland
Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland
Evang Kliniken Essen Mitte Essen Germany
Global Product Development Medical Affairs F Hoffmann La Roche Basel Switzerland
Institut Bergonie Early Phase Trials and Sarcoma Units Bordeaux France
Izmir University of Economics Medical Point Hospital Izmir Türkiye
Masaryk Memorial Cancer Institute Brno Czech Republic
Medical Faculty University of Zurich Zurich Switzerland
Medical Oncology Department Hospital de Sant Joan Despí Moisès Broggi ICO Hospitalet Barcelona Spain
Medical Oncology Department Miguel Servet University Hospital Zaragoza Spain
Pathology Group Foundation Medicine Cambridge MA USA
Upstate Medical University Departments of Pathology Urology and Medicine Syracuse NY USA
Citace poskytuje Crossref.org
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