Portal de investigación
STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP)
Fecha de publicación:
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Autores organización
Autores
- Cordeiro de Lima VC
- Corassa M
- Saldanha E
- Freitas H
- Arrieta O
- Raez L
- Samtani S
- Ramos M
- Rojas C
- Burotto M
- Chamorro DF
- Recondo G
- Ruiz-Patiño A
- Más L
- Zatarain-Barrón L
- Mejía S
- Nicolas Minata J
- Martín C
- Bautista Blaquier J
- Motta Guerrero R
- Aliaga-Macha C
- Carracedo C
- Ordóñez-Reyes C
- Garcia-Robledo JE
- Corrales L
- Sotelo C
- Ricaurte L
- Santoyo N
- Cuello M
- Jaller E
- Rodríguez J
- Archila P
- Bermudez M
- Gamez T
- Russo A
- Viola L
- Malapelle U
- de Miguel Perez D
- Rolfo C
- Rosell R
Grupos de investigación
Resumen
Background: Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. Methods: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients’ tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). Results: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3–5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 = 50% (30.9 months), and different from those with PD-L1 1–49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. Conclusions: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS. © 2022 The Authors
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 0169-5002, 1872-8332
- Tipo:
- Article
- Páginas:
- 114-121
- Enlace a otro recurso:
- www.scopus.com
Lung Cancer Elsevier Ireland Ltd
Citas Recibidas en Web of Science: 10
Citas Recibidas en Scopus: 28
Documentos
- No hay documentos
Filiaciones
Keywords
- AMP-Activated Protein Kinase Kinases; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Hispanic or Latino; Humans; Kelch-Like ECH-Associated Protein 1; Lung Neoplasms; Mutation; NF-E2-Related Factor 2; Prognosis; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins p21(ras); Registries; Retrospective Studies; immune checkpoint inhibitor; kelch like ECH associated protein 1; programmed death 1 ligand 1; protein kinase LKB1; KEAP1 protein, human; kelch like ECH associated protein 1; programmed death 1 ligand 1; protein p21; STK11 protein, human; transcription factor Nrf2; tumor marker; adrenal insufficiency; adult; aged; arthralgia; Article; cohort analysis; diabetes mellitus; diarrhea; fatigue; female; gene expression level; gene mutation; human; hypothyroidism; interstitial nephritis; KEAP1 gene; liver toxicity; major clinical study; male; myalgia; nausea; non small cell lung cancer; oncogene K ras; overall survival; progression free survival; psoriasis; rash; ret
Proyectos asociados
EFECTO DEL EXTRACTO DE Trametes versicolor SOBRE EL FENOTIPO Y LA FUNCIÓN DE CÉLULAS DENDRÍTICAS HUMANAS CONDICIONADAS CON MEDIOS DE CÉLULAS DE CARCINOMA ORAL
Investigador Principal: ANDRES FELIPE CARDONA MENDOZA
PCI-2019-10805 . 2020
Citar la publicación
Cordeiro de Lima VC,Corassa M,Saldanha E,Freitas H,Arrieta O,Raez L,Samtani S,Ramos M,Rojas C,Burotto M,Chamorro DF,Recondo G,Ruiz A,Más L,Zatarain L,Mejía S,Nicolas J,Martín C,Bautista J,Motta R,Aliaga C,Carracedo C,Ordóñez C,Garcia JE,Corrales L,Sotelo C,Ricaurte L,Santoyo N,Cuello M,Jaller E,Rodríguez J,Archila P,Bermudez M,Gamez T,Russo A,Viola L,Malapelle U,de Miguel D,Rolfo C,Rosell R,Cardona AF. STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP). Lung Cancer. 2022. 170. p. 114-121. IF:5,300. (2).