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

Westphalen, CB; Federer-Gsponer, J; Pauli, C; Karapetyan, AR; Chalabi, N; Duran-Pacheco, G; Beringer, A; Bochtler, T; Cook, N; Hoglander, E; Jin, DX; Losa, F; Mileshkin, L; Moch, H; Ross, JS; Sokol, ES; Tothill, RW; Kramer, A

Author(s): Westphalen, CB; Federer-Gsponer, J; Pauli, C; Karapetyan, AR; Chalabi, N; Duran-Pacheco, G; Beringer, A; Bochtler, T; Cook, N; Hoglander, E; Jin, DX; Losa, F; Mileshkin, L; Moch, H; Ross, JS; Sokol, ES; Tothill, RW; Kramer, A;
Details: Publication Year 2023-11-01,Volume 8,Issue #6,Page 102035
Journal Title: ESMO Open
Publication Type: Research article
Abstract: BACKGROUND: Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of approximately 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, approximately 32% of patients carried a potentially targetable genomic alteration, including PIK3CA, FGFR2, ERBB2, BRAF(V600E), 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.
Keywords: genomic profiling; molecular targeted therapy; neoplasms; precision medicine; unknown primary
Department(s): Medical Oncology
PubMed ID: 37922692
Publisher's Version: https://doi.org/10.1016/j.esmoop.2023.102035
Open Access at Publisher's Site: https://doi.org/10.1016/j.esmoop.2023.102035
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-04 02:56:48

Last Modified: 2024-01-04 02:57:34