TY  - JOUR
AU  - Nasca, Vincenzo
AU  - Zhao, Joseph
AU  - Ros, Javier
AU  - Lonardi, Sara
AU  - Zwart, Koen
AU  - Cohen, Romain
AU  - Fakih, Marwan
AU  - Jayachandran, Priya
AU  - Roodhart, Jeanine M L
AU  - Derksen, Jeroen
AU  - Intini, Rossana
AU  - Bergamo, Francesca
AU  - Mazzoli, Giacomo
AU  - Ghelardi, Filippo
AU  - Ligero, Marta
AU  - Jonnagaddala, Jitendra
AU  - Hawkins, Nicholas
AU  - Ward, Robyn L
AU  - Wankhede, Durgesh
AU  - Brenner, Hermann
AU  - Hoffmeister, Michael
AU  - Vitellaro, Marco
AU  - Salvatore, Lisa
AU  - Gallois, Claire
AU  - Laurent-Puig, Pierre
AU  - Cremolini, Chiara
AU  - Overman, Michael J
AU  - Taieb, Julien
AU  - Tougeron, David
AU  - Andre, Thierry
AU  - Kather, Jakob Nikolas
AU  - Sundar, Raghav
AU  - Carmona, Javier
AU  - Elez, Elena
AU  - Koopman, Miriam
AU  - Pietrantonio, Filippo
TI  - Sex and outcomes of patients with microsatellite instability-high and BRAF V600E mutated metastatic colorectal cancer receiving immune checkpoint inhibitors.
JO  - Journal for ImmunoTherapy of Cancer
VL  - 13
IS  - 2
SN  - 2051-1426
CY  - London
PB  - BioMed Central
M1  - DKFZ-2025-00333
SP  - e010598
PY  - 2025
AB  - 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
KW  - Humans
KW  - Colorectal Neoplasms: drug therapy
KW  - Colorectal Neoplasms: genetics
KW  - Colorectal Neoplasms: pathology
KW  - Microsatellite Instability
KW  - Immune Checkpoint Inhibitors: therapeutic use
KW  - Immune Checkpoint Inhibitors: pharmacology
KW  - Male
KW  - Proto-Oncogene Proteins B-raf: genetics
KW  - Female
KW  - Middle Aged
KW  - Aged
KW  - Mutation
KW  - Sex Factors
KW  - Neoplasm Metastasis
KW  - Adult
KW  - Colorectal Cancer (Other)
KW  - Immune Checkpoint Inhibitor (Other)
KW  - Microsatellite (Other)
KW  - Mismatch repair - MMR (Other)
KW  - Immune Checkpoint Inhibitors (NLM Chemicals)
KW  - Proto-Oncogene Proteins B-raf (NLM Chemicals)
KW  - BRAF protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39929672
DO  - DOI:10.1136/jitc-2024-010598
UR  - https://inrepo02.dkfz.de/record/298888
ER  -