BRAF V600E / RAS Mutations and Lynch Syndrome in Patients With MSI-H/dMMR Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors

We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS / BRAF V600E mutations and Lynch syndrome (LS). Patients were defined as LS-linked...

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Detalhes bibliográficos
Autores: Colle, Raphael, Lonardi, Sara|||0000-0002-7593-8138, Cachanado, Marine|||0000-0002-9739-7950, Overman, Michael J, Elez, Elena|||0000-0002-4653-6324, Fakih, Marwan|||0000-0002-6554-5488, Corti, Francesca, Jayachandran, Priya, Svrcek, Magali, Dardenne, Antoine, Cervantes, Baptiste, Duval, Alex, Cohen, Romain|||0000-0001-9602-5162, Pietrantonio, Filippo|||0000-0002-8530-8420, André, Thierry|||0000-0002-5103-7095
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:320154
Acesso em linha:https://ddd.uab.cat/record/320154
https://dx.doi.org/urn:doi:10.1093/oncolo/oyad082
Access Level:acceso abierto
Palavra-chave:Deficient mismatch repair
Metastatic colorectal cancer
Immune checkpoint inhibitors
Lynch syndrome
RAS mutation
BRAF mutation
Descrição
Resumo:We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS / BRAF V600E mutations and Lynch syndrome (LS). Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAF V600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P <.2) if limited number of events. Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 in the total population, 111 (24.0%) were treated in first-line; 129 (28.8%) were BRAF V600E -mutated and 153 (32.8%) RAS -mutated. Median follow-up was 20.9 months. In adjusted analysis of the whole population (PFS/OS events = 186/133), no associations with PFS and OS were observed for BRAF V600E -mutated (PFS HR= 1.20, P =.372; OS HR = 1.06, P =.811) and RAS -mutated patients (PFS HR = 0.93, P =.712, OS HR = 0.75, P =.202). In adjusted analysis in the Lynch/sporadic status-assigned population (n = 242; PFS/OS events = 80/54), LS-liked patients had an improved PFS compared to sporadic cases (HR = 0.49, P =.036). The adjusted HR for OS was 0.56 with no significance (P =.143). No adjustment on BRAF V600E mutation was done due to collinearity. In this cohort, RAS/BRAF V600E mutations were not associated with survival while LS conferred an improved PFS. Using data from 2 cohorts of patients with MSI/dMMR metastatic colorectal cancer treated with immune checkpoint inhibitors, this study evaluated the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome.

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