Portal de investigación
Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes
Fecha de publicación:
Fecha Ahead of Print:
Autores organización
Autores
- Caballé-Perez E
- Hernández-Pedro N
- Ramos-Ramírez M
- Barrios-Bernal P
- Romero-Núñez E
- Lucio-Lozada J
- Ávila-Ríos S
- Reyes-Terán G
- Arrieta O
Grupos de investigación
Resumen
Purpose: Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10–40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited. Methods: A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023. Results: KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRASG12D (n = 16, 32%) and KRASG12C (n = 16, 32%) represented the most prevalent subtypes. KRASG12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRASG12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23–17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16–0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08–0.70; p = 0.009). Conclusions: To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings. © 2023, The Author(s).
© 2023. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 1699-048X, 1699-3055
- Tipo:
- Article
- Páginas:
- 836-850
- Enlace a otro recurso:
- www.scopus.com
CLINICAL & TRANSLATIONAL ONCOLOGY Springer Science and Business Media Deutschland GmbH
Citas Recibidas en Scopus: 3
Documentos
- No hay documentos
Filiaciones
Keywords
- Comutations; Immunotherapy; KRAS G12D; Non-small cell lung carcinoma; STK11; TP53
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Citar la publicación
Caballé E,Hernández N,Ramos M,Barrios P,Romero E,Lucio J,Ávila S,Reyes G,Cardona AF,Arrieta O. Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes. Clin Transl Oncol. 2023. 26. (4):p. 836-850. IF:2,800. (2).