Clinical impact of STK11 mutation in advanced-stage non-small cell lung cancer.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 14 03 2022
accepted: 10 05 2022
pubmed: 28 6 2022
medline: 17 8 2022
entrez: 27 6 2022
Statut: ppublish

Résumé

Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC). The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation. The secondary objective is to assess time to treatment failure (TTF) for the first-line chemotherapy or immunotherapy. This observational multicentric study was conducted in Nouvelle-Aquitaine (France), for 24 months. Clinical, histopathological and imagery data were collected in each centre while the next-generation sequencing analysis was performed in Bordeaux Hospital University. Patient's data were longitudinally followed from NSCLC diagnosis date to the occurrence of censoring events (therapeutic failure or death, as applicable) or until the study end date. median OS from the first drug administration was significantly longer for STK11 The presence of STK11 mutation is associated with poor prognosis in NSCLC.

Sections du résumé

BACKGROUND
Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC).
OBJECTIVE
The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation. The secondary objective is to assess time to treatment failure (TTF) for the first-line chemotherapy or immunotherapy.
METHODS
This observational multicentric study was conducted in Nouvelle-Aquitaine (France), for 24 months. Clinical, histopathological and imagery data were collected in each centre while the next-generation sequencing analysis was performed in Bordeaux Hospital University. Patient's data were longitudinally followed from NSCLC diagnosis date to the occurrence of censoring events (therapeutic failure or death, as applicable) or until the study end date.
RESULTS
median OS from the first drug administration was significantly longer for STK11
CONCLUSION
The presence of STK11 mutation is associated with poor prognosis in NSCLC.

Identifiants

pubmed: 35759814
pii: S0959-8049(22)00305-7
doi: 10.1016/j.ejca.2022.05.026
pii:
doi:

Substances chimiques

Protein Serine-Threonine Kinases EC 2.7.11.1
STK11 protein, human EC 2.7.11.1
AMP-Activated Protein Kinase Kinases EC 2.7.11.3

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

85-95

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PR, SA, CC, SGG, RV, AG, AC, LN, JPM, JB and POG have no conflicts of interest to disclose. CD has received consulting fees or honorarium from Astra-Zeneca, BMS, and accommodation and travelling expenses for meetings from Astra-Zeneca, BMS, PSD, Pfizer and Roche.

Auteurs

Pietro Rosellini (P)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France.

Samuel Amintas (S)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France; Univ. Bordeaux, Inserm CIC1401, Inserm CR1219, Inserm U1035, F-33000 Bordeaux, France.

Charline Caumont (C)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France.

Rémi Veillon (R)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France.

Sigolène Galland-Girodet (S)

Polyclinique Bordeaux Nord Aquitaine, F-33000 Bordeaux, France.

Alain Cuguillière (A)

Bagatelle Hôpital d'instruction des Armées, F-33000 Villenave-d'Ornon, France.

Laurent Nguyen (L)

Clinique Saint Augustin, F-33000 Bordeaux, France.

Charlotte Domblides (C)

Department of Medical Oncology, Hôpital Saint-André, CHU Bordeaux-University of Bordeaux, F-33000 Bordeaux, France; ImmunoConcEpt, CNRS UMR 5164, Bordeaux University, F-33000 Bordeaux, France.

Amandine Gouverneur (A)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France; Univ. Bordeaux, Inserm CIC1401, Inserm CR1219, Inserm U1035, F-33000 Bordeaux, France.

Jean-Philippe Merlio (JP)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France; Univ. Bordeaux, Inserm CIC1401, Inserm CR1219, Inserm U1035, F-33000 Bordeaux, France.

Julien Bezin (J)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France; Univ. Bordeaux, Inserm CIC1401, Inserm CR1219, Inserm U1035, F-33000 Bordeaux, France.

Pierre-Olivier Girodet (PO)

CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France; Univ. Bordeaux, Inserm CIC1401, Inserm CR1219, Inserm U1035, F-33000 Bordeaux, France. Electronic address: pierre-olivier.girodet@u-bordeaux.fr.

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Classifications MeSH