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Baseline mutational profiles of patients with carcinoma of unknown primary origin enrolled in the CUPISCO study☆

Background - Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of ∼1 year or less, stressing the need for more tailored treatments, which are currently being tested in clinical trials. CUPISCO (NCT03498521) was a phase II randomized study of targete...

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Main Authors: Westphalen, Christoph Benedikt (Author) , Federer-Gsponer, Joël (Author) , Pauli, C. (Author) , Karapetyan, A. R. (Author) , Chalabi, N. (Author) , Durán-Pacheco, G. (Author) , Beringer, A. (Author) , Bochtler, Tilmann (Author) , Cook, N. (Author) , Höglander, E. (Author) , Jin, D. X. (Author) , Losa, F. (Author) , Mileshkin, L. (Author) , Moch, H. (Author) , Ross, J. S. (Author) , Sokol, E. S. (Author) , Tothill, R. W. (Author) , Krämer, Alwin (Author)
Format: Article (Journal)
Language:English
Published: December 2023
In: ESMO open
Year: 2023, Volume: 8, Issue: 6, Pages: 1-9
ISSN:2059-7029
DOI:10.1016/j.esmoop.2023.102035
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.esmoop.2023.102035
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2059702923012760
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Author Notes:C. B. Westphalen, J. Federer-Gsponer, C. Pauli, A. R. Karapetyan, N. Chalabi, G. Durán-Pacheco, A. Beringer, T. Bochtler, N. Cook, E. Höglander, D. X. Jin, F. Losa, L. Mileshkin, H. Moch, J. S. Ross, E. S. Sokol, R. W. Tothill & A. Krämer
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Summary:Background - Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of ∼1 year or less, stressing the need for more tailored treatments, which are currently being tested in clinical trials. CUPISCO (NCT03498521) was a phase II randomized study of targeted therapy/cancer immunotherapy versus platinum-based chemotherapy in patients with previously untreated, unfavorable CUP, defined as per the European Society for Medical Oncology guidelines. We present a preliminary, descriptive molecular analysis of 464 patients with stringently diagnosed, unfavorable CUP enrolled in the CUPISCO study. - Materials and methods - Genomic profiling was carried out on formalin-fixed, paraffin-embedded tissue to detect genomic alterations and assess tumor mutational burden and microsatellite instability. - Results - Overall, ∼32% of patients carried a potentially targetable genomic alteration, including PIK3CA, FGFR2, ERBB2, BRAFV600E, EGFR, MET, NTRK1, ROS1, and ALK. Using hierarchical clustering of co-mutational profiles, 10 clusters were identified with specific genomic alteration co-occurrences, with some mirroring defined tumor entities. - Conclusions - Results reveal the molecular heterogeneity of patients with unfavorable CUP and suggest that genomic profiling may be used as part of informed decision-making to identify the potential primary tumor and targeted treatment options. Whether stringently diagnosed patients with unfavorable CUP benefit from targeted therapies in a similar manner to those with matched known primaries will be a key learning from CUPISCO.
Item Description:Online veröffentlicht am 2 November 2023
Gesehen am 23.04.2024
Physical Description:Online Resource
ISSN:2059-7029
DOI:10.1016/j.esmoop.2023.102035

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