Baseline mutational profiles of patients with carcinoma of unknown primary origin enrolled in the CUPISCO study.
ESMO Open
; 8(6): 102035, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37922692
ABSTRACT
BACKGROUND:
Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of â¼1 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 ANDMETHODS:
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, â¼32% 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Primárias Desconhecidas
/
Carcinoma
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article