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

被引：24

作者：

Colle, Raphael ^{[1
,2
,3
,4
]}

Lonardi, Sara ^{[5
]}

Cachanado, Marine ^{[3
,4
]}

Overman, Michael J. ^{[6
]}

Elez, Elena ^{[7
]}

Fakih, Marwan ^{[8
]}

Corti, Francesca ^{[9
]}

Jayachandran, Priya ^{[10
]}

Svrcek, Magali ^{[2
,11
]}

Dardenne, Antoine ^{[1
]}

Cervantes, Baptiste ^{[1
]}

Duval, Alex ^{[2
,3
,4
]}

Cohen, Romain ^{[1
,2
,3
,4
]}

Pietrantonio, Filippo ^{[9
]}

Andre, Thierry ^{[1
,2
,3
,4
]}

机构：

[1] Sorbonne Univ, St Antoine Hosp, AP HP, Dept Med Oncol, Paris, France

[2] Sorbonne Univ, Ctr Rech St Antoine, Unite Mixte Rech Sci 938,INSERM,Equipe Labellisee, Equipe Instabil Microsatellites & Canc,SIRIC CURA, Paris, France

[3] Sorbonne Univ, Dept Clin Pharmacol, St Antoine Hosp, Assistance Publ Hop Paris, Paris, France

[4] Sorbonne Univ, St Antoine Hosp, Assistance Publ Hop Paris, Clin Res Platform Paris East URCEST CRC CRB, Paris, France

[5] Ist Oncol Veneto IOV IRCSS, Oncol Dept, Padua, Italy

[6] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Oncol, Houston, TX USA

[7] Univ Autonoma Barcelona, Dept Med Oncol, Vall dHebron Inst Oncol VHIO, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

[8] City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA

[9] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[10] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Div Med Oncol, Los Angeles, CA USA

[11] Sorbonne Univ, St Antoine Hosp, AP HP, Dept Pathol, Paris, France

来源：

ONCOLOGIST | 2023年 / 28卷 / 09期

关键词：

deficient mismatch repair; metastatic colorectal cancer; immune checkpoint inhibitors; Lynch syndrome; RAS mutation; BRAF mutation; MISMATCH REPAIR-DEFICIENT; OPEN-LABEL; NIVOLUMAB;

D O I：

10.1093/oncolo/oyad082

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background 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 and Methods 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. Results 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. Conclusion 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.

引用

页码：771 / 779

页数：9

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