The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and their influence on the NLR in NSCLC patients treated with immunotherapy.

Immunotherapy KEAP1 KRAS NSCLC STK11

Journal

Cancer treatment and research communications
ISSN: 2468-2942
Titre abrégé: Cancer Treat Res Commun
Pays: England
ID NLM: 101694651

Informations de publication

Date de publication:
10 Oct 2023
Historique:
received: 25 09 2022
revised: 23 08 2023
accepted: 08 10 2023
medline: 14 10 2023
pubmed: 14 10 2023
entrez: 13 10 2023
Statut: aheadofprint

Résumé

PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method. From 100 patients with known KRAS status, 50 were mutated (KRAS STK11 Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism.

Sections du résumé

BACKGROUND BACKGROUND
PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs.
PATIENTS & METHODS METHODS
This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method.
RESULTS RESULTS
From 100 patients with known KRAS status, 50 were mutated (KRAS
CONCLUSION CONCLUSIONS
STK11
MICROABSTRACT CONCLUSIONS
Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism.

Identifiants

pubmed: 37832364
pii: S2468-2942(23)00089-8
doi: 10.1016/j.ctarc.2023.100767
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100767

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Francis Proulx-Rocray (F)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada.

Bertrand Routy (B)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada; Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Rami Nassabein (R)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada.

Wiam Belkaid (W)

Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Danh Tran-Thanh (D)

Pathology Department, Centre Hospitalier de l'Université de Montréal, 1051 Sanguinet Street, Montreal, QC, Canada.

Julie Malo (J)

Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Marion Tonneau (M)

Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Omar El Ouarzadi (OE)

Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Marie Florescu (M)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada; Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Mustapha Tehfe (M)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada; Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada.

Normand Blais (N)

Medical Oncology Department, Centre Hospitalier de l'Université de Montréal (CHUM), 1051 Sanguinet Street, Montreal, QC, Canada; Department of Medicine, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, 900 Saint-Denis Street, Montreal, QC, Canada. Electronic address: normand.blais.chum@ssss.gouv.qc.ca.

Classifications MeSH