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 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, BRAF

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.

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure CBW reports honoraria from Bayer, Celgene, Ipsen, Servier, Taiho, and F. Hoffmann-La Roche Ltd, has participated in advisory boards for Celgene, Shire/Baxalta, Rafael Pharmaceuticals, RedHill BioPharma, and F. Hoffmann-La Roche Ltd, and has received travel/accommodation expenses from Bayer, Celgene, RedHill BioPharma, F. Hoffmann-La Roche Ltd, Servier, and Taiho. JFG is an employee of and has stocks/shares in F. Hoffmann-La Roche Ltd. CP has received an institutional research grant from F. Hoffmann-La Roche Ltd, works as a study pathologist for the CUPISCO trial, and has received travel coverage and remuneration for study-related work such as histopathology reviews for patients in screening and in molecular tumor boards, for the benefit of her employer. ARK, NCh, and GDP are employees of and hold stocks/shares in F. Hoffmann-La Roche Ltd. AB was an employee of F. Hoffmann-La Roche Ltd. TB has received an institutional research grant from F. Hoffmann-La Roche Ltd, works as a study oncologist for the CUPISCO trial, and has received coverage for study-related travel and remuneration for study-related work in a molecular tumor board for the benefit of his employer. NCo has participated in an advisory board for RedX Pharmaceuticals and has received institutional research funding from AstraZeneca, Orion, F. Hoffmann-La Roche Ltd, Taiho, GSK, Novartis, Starpharma, Bayer, Eisai, UCB, RedX Pharmaceuticals, Stemline Therapeutics, Boehringer Ingelheim, Merck, Avacta Pharmaceuticals, and Tarveda Therapeutics. EH is an employee of and holds stocks/shares in F. Hoffmann-La Roche Ltd. DXJ is an employee of Foundation Medicine, Inc. and holds stocks/shares in F. Hoffmann-La Roche Ltd. FL has received institutional research funding from F. Hoffmann-La Roche Ltd, Amgen, and Merck, has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd and Merck, has participated in an advisory board for F. Hoffmann-La Roche Ltd, Amgen, Merck, Sanofi, and Servier, and has participated in a speaker bureau/expert testimony for F. Hoffmann-La Roche Ltd and Sanofi. LM has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd and BeiGene. HM has received honoraria from or has participated in advisory boards for F. Hoffmann-La Roche Ltd, Ventana, Definiens, Merck, BMS, Astellas, Johnson & Johnson, Bayer, Ipsen, and Amgen, has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd and Definiens, and has received institutional research funding from F. Hoffmann-La Roche Ltd. JSR has received honoraria from, holds stocks/shares in, and has a leadership role in Foundation Medicine, Inc. ESS is an employee of Foundation Medicine, Inc. and holds stocks/shares in F. Hoffmann-La Roche Ltd. RWT has received honoraria from Merck Serono Australia. AK has received honoraria from F. Hoffmann-La Roche Ltd, Daiichi Sankyo, and AbbVie, honoraria to his institution from F. Hoffmann-La Roche Ltd and Bayer, has a leadership role in F. Hoffmann-La Roche Ltd, has received institutional research funding from Merck and Bayer, has received travel/accommodation expenses from F. Hoffmann-La Roche Ltd, Celgene, and Daiichi Sankyo, and has acted as an advisory consultant for Daiichi Sankyo, BMS, and AbbVie. All authors received research support (medical writing support) from F. Hoffmann-La Roche Ltd.