BRAF V600E / RAS Mutations and Lynch Syndrome in Patients With MSI-H/dMMR Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors
Colle, Raphael (Saint-Antoine Hospital, AP-HP (Paris, França))
Lonardi, Sara (Istituto Oncologico Veneto IOV-IRCSS, Padua, Italy.)
Cachanado, Marine (Sorbonne University (Paris))
Overman, Michael J (University of Texas MD Anderson Cancer Center (Houston, Estats Units di'Amèrica))
Elez, Elena (Hospital Universitari Vall d'Hebron)
Fakih, Marwan (City of Hope Comprehensive Cancer Center (Duarte, Estats Units d'Amèrica))
Corti, Francesca (Fondazione IRCCS Istituto Nazionale dei Tumori (Milan, Itàlia))
Jayachandran, Priya (University of Southern California (Los Angeles, Estats Units d'Amèrica))
Svrcek, Magali (Sorbonne University (Paris))
Dardenne, Antoine (Sorbonne University (Paris))
Cervantes, Baptiste (Sorbonne University (Paris))
Duval, Alex (Sorbonne University (Paris))
Cohen, Romain (Sorbonne University (Paris))
Pietrantonio, Filippo (Fondazione IRCCS Istituto Nazionale dei Tumori (Milan, Itàlia))
André, Thierry (Sorbonne University (Paris))
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Deficient mismatch repair ; Metastatic colorectal cancer ; Immune checkpoint inhibitors ; Lynch syndrome ; RAS mutation ; BRAF mutation
Publicat a:	The Oncologist, Vol. 28 (april 2023) , p. 771-779, ISSN 1549-490X

DOI: 10.1093/oncolo/oyad082
PMID: 37023721

9 p, 579.5 KB

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