%0 Journal Article
%A Nasca, Vincenzo
%A Zhao, Joseph
%A Ros, Javier
%A Lonardi, Sara
%A Zwart, Koen
%A Cohen, Romain
%A Fakih, Marwan
%A Jayachandran, Priya
%A Roodhart, Jeanine M L
%A Derksen, Jeroen
%A Intini, Rossana
%A Bergamo, Francesca
%A Mazzoli, Giacomo
%A Ghelardi, Filippo
%A Ligero, Marta
%A Jonnagaddala, Jitendra
%A Hawkins, Nicholas
%A Ward, Robyn L
%A Wankhede, Durgesh
%A Brenner, Hermann
%A Hoffmeister, Michael
%A Vitellaro, Marco
%A Salvatore, Lisa
%A Gallois, Claire
%A Laurent-Puig, Pierre
%A Cremolini, Chiara
%A Overman, Michael J
%A Taieb, Julien
%A Tougeron, David
%A Andre, Thierry
%A Kather, Jakob Nikolas
%A Sundar, Raghav
%A Carmona, Javier
%A Elez, Elena
%A Koopman, Miriam
%A Pietrantonio, Filippo
%T Sex and outcomes of patients with microsatellite instability-high and BRAF V600E mutated metastatic colorectal cancer receiving immune checkpoint inhibitors.
%J Journal for ImmunoTherapy of Cancer
%V 13
%N 2
%@ 2051-1426
%C London
%I BioMed Central
%M DKFZ-2025-00333
%P e010598
%D 2025
%X Immune checkpoint inhibitors (ICIs) are the gold standard therapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A significant proportion of patients show resistance, making the identification of determinants of response crucial. Growing evidence supports the role of sex in determining susceptibility to anticancer therapies, but data is lacking for patients with MSI-H CRC.In this real-world cohort comprising 624 patients with MSI-H mCRC receiving ICIs, we investigated the impact of sex on patients' outcomes, overall and according to RAS-BRAF mutational status or type of treatment (anti-PD-(L)1 with or without anti-CTLA-4 agents). We then investigated these associations also in two independent cohorts of patients with early-stage or advanced MSI-H CRC unexposed to ICIs. Finally, we explored two public microarray and RNA-seq datasets from patients with non-metastatic or metastatic MSI-H CRC to gain translational insights on the association between sex, BRAF status and immune contextures/ICI efficacy.Although no differences were observed between females and males either overall or in the BRAF wild-type cohort, male sex was associated with inferior progression-free survival (PFS) and overall survival (OS) in the BRAF mutated cohort (in multivariable models, HR for PFS: 1.79, 95
%K Humans
%K Colorectal Neoplasms: drug therapy
%K Colorectal Neoplasms: genetics
%K Colorectal Neoplasms: pathology
%K Microsatellite Instability
%K Immune Checkpoint Inhibitors: therapeutic use
%K Immune Checkpoint Inhibitors: pharmacology
%K Male
%K Proto-Oncogene Proteins B-raf: genetics
%K Female
%K Middle Aged
%K Aged
%K Mutation
%K Sex Factors
%K Neoplasm Metastasis
%K Adult
%K Colorectal Cancer (Other)
%K Immune Checkpoint Inhibitor (Other)
%K Microsatellite (Other)
%K Mismatch repair - MMR (Other)
%K Immune Checkpoint Inhibitors (NLM Chemicals)
%K Proto-Oncogene Proteins B-raf (NLM Chemicals)
%K BRAF protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39929672
%R 10.1136/jitc-2024-010598
%U https://inrepo02.dkfz.de/record/298888